Publication date: Available online 31 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Elizabeth R Felix, Diana D. Cardenas, Thomas N. Bryce, Susan Charlifue, Tae Kyong Lee, Bria MacIntyre, Sara Mulroy, Heather Taylor
Publication date: Available online 31 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Elizabeth R Felix, Diana D. Cardenas, Thomas N. Bryce, Susan Charlifue, Tae Kyong Lee, Bria MacIntyre, Sara Mulroy, Heather Taylor
Publication date: Available online 31 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Elizabeth R Felix, Diana D. Cardenas, Thomas N. Bryce, Susan Charlifue, Tae Kyong Lee, Bria MacIntyre, Sara Mulroy, Heather Taylor
Publication date: Available online 31 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Elizabeth R Felix, Diana D. Cardenas, Thomas N. Bryce, Susan Charlifue, Tae Kyong Lee, Bria MacIntyre, Sara Mulroy, Heather Taylor
Publication date: Available online 31 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Elizabeth R Felix, Diana D. Cardenas, Thomas N. Bryce, Susan Charlifue, Tae Kyong Lee, Bria MacIntyre, Sara Mulroy, Heather Taylor
Publication date: Available online 31 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Elizabeth R Felix, Diana D. Cardenas, Thomas N. Bryce, Susan Charlifue, Tae Kyong Lee, Bria MacIntyre, Sara Mulroy, Heather Taylor
Publication date: Available online 31 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Elizabeth R Felix, Diana D. Cardenas, Thomas N. Bryce, Susan Charlifue, Tae Kyong Lee, Bria MacIntyre, Sara Mulroy, Heather Taylor
Publication date: Available online 31 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Elizabeth R Felix, Diana D. Cardenas, Thomas N. Bryce, Susan Charlifue, Tae Kyong Lee, Bria MacIntyre, Sara Mulroy, Heather Taylor
Publication date: Available online 31 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Elizabeth R Felix, Diana D. Cardenas, Thomas N. Bryce, Susan Charlifue, Tae Kyong Lee, Bria MacIntyre, Sara Mulroy, Heather Taylor
Publication date: Available online 31 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Elizabeth R Felix, Diana D. Cardenas, Thomas N. Bryce, Susan Charlifue, Tae Kyong Lee, Bria MacIntyre, Sara Mulroy, Heather Taylor
Publication date: Available online 31 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Elizabeth R Felix, Diana D. Cardenas, Thomas N. Bryce, Susan Charlifue, Tae Kyong Lee, Bria MacIntyre, Sara Mulroy, Heather Taylor
Disrupted pain regulation has been proposed as a component in functional somatic disorders (FSD). The objective of this study was to examine a general population sample, encompassing three delimitations of FSD while assessing pain sensitivity and conditioning pain modulation (CPM).
Pressure pain thresholds (PPTs) at the tibialis and trapezius muscles were recorded at baseline. During cold pressor stimulation of the hand, the tibialis PPTs were re-assessed and the difference from baseline measures defined the CPM effect. Participants (n=2,198, 53% females) were randomly selected from the adult Danish population. FSD was established by self-reported symptom questionnaires.
With a few exceptions, only weak associations were seen between PPTs and CPM in cases with FSD (p>0.1). A high PPT was associated with lower odds of having multi-organ bodily distress syndrome (ORPPT trapezius: 0.66, 95% CI: 0.49-0.88, p=0.005), with the symptom profile characterized by all symptoms (ORPPT trapezius: 0.72, 95% CI: 0.58-0.90, p=0.003 and ORPPT tibialis: 0.75, 95% CI: 0.62-0.91, p=0.004), and with multiple chemical sensitivity (ORPPT trapezius: 0.81, 95% CI: 0.67-0.97, p=0.022). High CPM was associated with high odds of having irritable bowel (ORCPM relative: 1.22, 95% CI: 1.04-1.43, p=0.013 and ORCPM absolute=2.66, 95% CI: 1.07-6.45, p=0.033). However, only PPT measured over the trapezius muscle were still significant after correction for multiple testing for the symptom profile characterized by all symptoms.
Findings from this study do not support altered pain regulation in questionnaire-based FSD which is in contrast with the existing presumption. Further epidemiological studies in this field are needed.
Disrupted pain regulation has been proposed as a component in functional somatic disorders (FSD). The objective of this study was to examine a general population sample, encompassing three delimitations of FSD while assessing pain sensitivity and conditioning pain modulation (CPM).
Pressure pain thresholds (PPTs) at the tibialis and trapezius muscles were recorded at baseline. During cold pressor stimulation of the hand, the tibialis PPTs were re-assessed and the difference from baseline measures defined the CPM effect. Participants (n=2,198, 53% females) were randomly selected from the adult Danish population. FSD was established by self-reported symptom questionnaires.
With a few exceptions, only weak associations were seen between PPTs and CPM in cases with FSD (p>0.1). A high PPT was associated with lower odds of having multi-organ bodily distress syndrome (ORPPT trapezius: 0.66, 95% CI: 0.49-0.88, p=0.005), with the symptom profile characterized by all symptoms (ORPPT trapezius: 0.72, 95% CI: 0.58-0.90, p=0.003 and ORPPT tibialis: 0.75, 95% CI: 0.62-0.91, p=0.004), and with multiple chemical sensitivity (ORPPT trapezius: 0.81, 95% CI: 0.67-0.97, p=0.022). High CPM was associated with high odds of having irritable bowel (ORCPM relative: 1.22, 95% CI: 1.04-1.43, p=0.013 and ORCPM absolute=2.66, 95% CI: 1.07-6.45, p=0.033). However, only PPT measured over the trapezius muscle were still significant after correction for multiple testing for the symptom profile characterized by all symptoms.
Findings from this study do not support altered pain regulation in questionnaire-based FSD which is in contrast with the existing presumption. Further epidemiological studies in this field are needed.
Nature, Published online: 27 July 2021; doi:10.1038/d41586-021-02063-y
Andrew Robinson reviews five of the week’s best science picks.
Neuropathic pain arises as a direct consequence of a lesion or disease affecting the somatosensory system. A number of preclinical studies have provided evidence for the involvement of cytokines, predominantly secreted by a variety of immune cells and by glial cells from the nervous system, in neuropathic pain conditions. Clinical trials and use of anti-cytokine drugs in different neuropathic etiologies support the relevance of cytokines as treatment targets. However, the use of such drugs, in particularly biotherapies, can provoke notable adverse effects. Moreover, it is challenging to select one given cytokine as target, among the various neuropathic pain conditions. It could thus be of interest to target other proteins, such as growth factors, in order to act more widely on the neuroinflammation network. Thus, platelet-rich plasma (PRP), an autologous blood concentrate, is known to contain a natural concentration of growth factors and immune system messengers and is widely used in the clinical setting for tissue regeneration and repair. In the present review, we critically assess the current knowledge on cytokines in neuropathic pain by taking into consideration both human studies and animal models. This analysis of the literature highlights the pathophysiological importance of cytokines. We particularly highlight the concept of time- and tissue- dependent cytokine activation during neuropathic pain conditions. Thus, direct or indirect cytokines modulation with biotherapies or growth factors appears relevant. In addition, we discuss therapeutic potential of localized injection of PRP as neuropathic pain treatment by pointing out the possible link between cytokines and the action of PRP.
The mechanisms underlying chronic phantom limb pain (PLP) are complex and insufficiently understood. Altered sensory thresholds are often associated with chronic pain but quantitative sensory testing (QST) in PLP has so far been inconclusive due to large methodological variation between studies and small sample sizes. In this study, we applied QST in 37 unilateral upper-limb amputees (23 with, 14 without PLP) and 19 healthy controls. We assessed heat pain (HPT), pressure pain (PPT), warmth detection (WDT), and two-point discrimination thresholds at the residual limb, a homologous point and the thenar of the intact limb as well as both corners of the mouth. We did not find significant differences in any of the thresholds between the groups. However, PLP intensity was negatively associated with HPT at all measured body sites except for the residual limb, indicating lower pain thresholds with higher PLP levels. Correlations between HPT and PLP were strongest in the contralateral face (r = -0.65, p < 0.001). Facial HPT were specifically associated with PLP, independent of residual limb pain (RLP) and various other covariates. HPT at the residual limb, however, were significantly associated with RLP, but not with PLP. We conclude that the association between PLP and, especially facial, HPT could be related to central mechanisms.
Women with Vulvodynia experience pain, related impacts on sex and daily functioning, and depression. While psychosocial factors are associated with outcomes in Vulvodynia, longitudinal data are limited, especially in mixed/spontaneous Vulvodynia. Broad psychological models such as Psychological Flexibility (PF) and content-specific factors such as body-exposure anxiety and avoidance during sexual activities (BEA), and perceived injustice, have not been adequately investigated in Vulvodynia. The aim of this study was to explore whether these factors assessed at baseline predict pain severity, pain-interference, sexual functioning and satisfaction, and depression three months later.
A longitudinal study of 349 women with Vulvodynia was conducted. Participants completed online self-report measures of pain-related and sexual outcomes, depression, BEA, perceived injustice, and facets of PF (present-moment-awareness, pain acceptance, committed action) at baseline and after three months, overlapping with the COVID-19 pandemic.
Seventy per cent of women responded at both assessments (n=244). There were significant decreases in pain severity, pain-interference, present-moment-awareness, committed action, and a significant increase in depression at three-months. All the baseline psychosocial factors significantly correlated with at least one outcome at three-months. When adjusting for baseline outcome and demographics, committed action significantly positively predicted depression at three-months, and pain acceptance significantly positively predicted pain-interference at three-months.
Among women with Vulvodynia, pain acceptance and committed action are prospectively associated with pain-interference and depression. The reliability and generalisability of these results needs to be established given the overlap with the COVID-19 pandemic. Future studies should investigate whether targeting these factors enhances outcomes in Vulvodynia.
The mechanism for reduced pain sensitivity associated with Alzheimer's disease (AD) has not been illustrated. We hypothesize that amyloid beta 1-42 (Aβ1-42) in the spinal cord acts as an endogenous analgesic peptide to suppress pain induced by nerve injury.
We used chronic constriction injury of the sciatic nerve (CCI) to produce neuropathic pain in Sprague-Dawley rats. ELISA and immunohistochemistry were used to determine the level of Aβ1-42, the expression of Wnt3a/5b, and glial activation in the spinal cord. Western blotting was used to determine the expression of interleukins, the phosphorylation of NR2B and ERK1/2, and the nuclear accumulation of transcriptional factors YAP/TAZ. Thermal hyperalgesia and mechanical allodynia were assessed after CCI and pharmacological manipulations through intrathecal administration.
Nerve injury increases spinal level of Aβ1-42, while intrathecal administration of MK-8931 reduces the level of Aβ1-42 and facilitates mechanical allodynia. Intrathecal administration of Aβ1-42 suppresses pain behaviors in the early and late phases of neuropathy. Spinal administration of Aβ1-42 regulates the expression of interleukins, reducing glial activation and phosphorylation of NR2B and ERK1/2 in the spinal cord of CCI rats. Furthermore, intrathecal administration of Aβ1-42 decreases Wnt5b expression and suppresses the nuclear accumulation of YAP and TAZ. Blocking the interaction between Aβ1-42 and Frizzled receptors by cSP5 reverses the analgesic effects of Aβ1-42.
These findings suggest that spinal Aβ1-42 acts as an endogenous analgesic peptide through regulating cytokines and Wnt pathways. This study may provide a potential target for the development of novel analgesic peptides.
Pain related to temporomandibular disorders (TMD) can be linked with multiple site pain (MSP), and may associate with increased pain sensitivity, more frequently among women than men. The aim of the study was to examine the associations of pressure pain threshold (PPT) and tolerance (PPTo) with TMD and associated MSP in the Northern Finland Birth Cohort 1966 (NFBC1966) study.
Altogether 1961 NFBC1966 subjects attended clinical medical and dental examination at the Institute of Dentistry, University of Oulu in 2012-2013. Clinical examinations were carried out using a modified Diagnostic Criteria for TMD protocol (DC/TMD). MSP was defined based on questions regarding body pain sites. Additionally, PPT and PPTo were assessed using algometer measurements. Mann-Whitney U-test and Tobit regression models were used to analyze associations between TMD sub-diagnoses, MSP, PPT, and PPTo, stratified by sex. Further models were adjusted with anxiety and depressive symptoms, which were assessed using Hopkins Symptom Checklist-25 (HSCL-25) and two-way interaction terms.
Among females, lower PPT and PPTo associated with myalgia and arthralgia. Among males, lower PPT and PPTo associated with MSP-linked TMD. Tobit regression analysis showed significantly lower PPT and PPTo values in the myalgia and arthralgia subgroups among female TMD subjects. Among females, disc displacement with reduction had an inverse association with PPT and PPTo. Among males, lower PPTo associated with degenerative joint disease and MSP-linked TMD.
The pain regulatory mechanisms behind TMD act differently between the sexes as local TMD among females and MSP-linked TMD among males associated with pain sensitivity.
The objective of this systematic review was to investigate the effectiveness of electrical stimulation (ES) for neck pain (NP).
The databases CINAHL, Embase, MEDLINE (via OVID), PEDro and Web of Science were searched, with no date restrictions. Two independent reviewers selected randomized controlled trials (RCTs) reporting pain, range of motion or psychosocial factors in people with NP, in which ES was applied. Methodological quality was assessed using the PEDro scale. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to evaluate the quality of evidence. Thirty studies met eligibility criteria.
Main results showed evidence of moderate quality that ES combined with other intervention significantly decreases the pain intensity compared to other intervention immediately post-treatment and at short-term follow-up; evidence of low quality showed significant effects of ES combined with other intervention in decreasing neck disability compared to other intervention immediately post-treatment; evidence of very-low quality that ES increased the pressure pain threshold compared to placebo immediately post-treatment and that ES + other intervention also increased the pressure pain threshold compared to other intervention at short-term follow-up.
ES combined with other intervention seems to be useful to relieve pain and to improve disability in people with NP, however more studies are needed.
Exposure to stressful experiences is often accompanied by suppressing pain perception, referred to as stress-induced analgesia. The neuropeptides orexins are essential in regulating the mechanism that responds to stressful and painful stimuli. Meanwhile, the ventral tegmental area (VTA), as a part of descending pain inhibitory system, responds to noxious stimuli. The present study aimed to investigate the role of intra-VTA administration of orexin receptor antagonists on stress-induced antinociceptive responses in the animal model of acute pain.
Ninety-three adult Wistar rats weighing 230–250 g were unilaterally implanted by a cannulae above the VTA. Animals were pretreated with different doses (1, 3, 10, and 30 nM/0.3 μl) of SB334867 as the orexin-1 receptor antagonist and TCS OX2 29 as the orexin-2 receptor antagonist into the VTA, just 5 min before 6 min exposure to forced swim stress (FSS). Nociceptive threshold was measured using the tail-flick test as a model of acute pain.
The results showed that exposure to FSS could significantly increase analgesic responses. Moreover, intra-VTA administration of SB334768 and TCS OX2 29 blocked the antinociceptive effect of FSS in the tail-flick test.
The findings suggest that OX1 and OX2 receptors in the VTA might modulate the antinociceptive behaviors induced by FSS in part.
Neuropathic pain arises as a direct consequence of a lesion or disease affecting the somatosensory system. A number of preclinical studies have provided evidence for the involvement of cytokines, predominantly secreted by a variety of immune cells and by glial cells from the nervous system, in neuropathic pain conditions. Clinical trials and use of anti-cytokine drugs in different neuropathic etiologies support the relevance of cytokines as treatment targets. However, the use of such drugs, in particularly biotherapies, can provoke notable adverse effects. Moreover, it is challenging to select one given cytokine as target, among the various neuropathic pain conditions. It could thus be of interest to target other proteins, such as growth factors, in order to act more widely on the neuroinflammation network. Thus, platelet-rich plasma (PRP), an autologous blood concentrate, is known to contain a natural concentration of growth factors and immune system messengers and is widely used in the clinical setting for tissue regeneration and repair. In the present review, we critically assess the current knowledge on cytokines in neuropathic pain by taking into consideration both human studies and animal models. This analysis of the literature highlights the pathophysiological importance of cytokines. We particularly highlight the concept of time- and tissue- dependent cytokine activation during neuropathic pain conditions. Thus, direct or indirect cytokines modulation with biotherapies or growth factors appears relevant. In addition, we discuss therapeutic potential of localized injection of PRP as neuropathic pain treatment by pointing out the possible link between cytokines and the action of PRP.
The mechanisms underlying chronic phantom limb pain (PLP) are complex and insufficiently understood. Altered sensory thresholds are often associated with chronic pain but quantitative sensory testing (QST) in PLP has so far been inconclusive due to large methodological variation between studies and small sample sizes. In this study, we applied QST in 37 unilateral upper-limb amputees (23 with, 14 without PLP) and 19 healthy controls. We assessed heat pain (HPT), pressure pain (PPT), warmth detection (WDT), and two-point discrimination thresholds at the residual limb, a homologous point and the thenar of the intact limb as well as both corners of the mouth. We did not find significant differences in any of the thresholds between the groups. However, PLP intensity was negatively associated with HPT at all measured body sites except for the residual limb, indicating lower pain thresholds with higher PLP levels. Correlations between HPT and PLP were strongest in the contralateral face (r = -0.65, p < 0.001). Facial HPT were specifically associated with PLP, independent of residual limb pain (RLP) and various other covariates. HPT at the residual limb, however, were significantly associated with RLP, but not with PLP. We conclude that the association between PLP and, especially facial, HPT could be related to central mechanisms.
Women with Vulvodynia experience pain, related impacts on sex and daily functioning, and depression. While psychosocial factors are associated with outcomes in Vulvodynia, longitudinal data are limited, especially in mixed/spontaneous Vulvodynia. Broad psychological models such as Psychological Flexibility (PF) and content-specific factors such as body-exposure anxiety and avoidance during sexual activities (BEA), and perceived injustice, have not been adequately investigated in Vulvodynia. The aim of this study was to explore whether these factors assessed at baseline predict pain severity, pain-interference, sexual functioning and satisfaction, and depression three months later.
A longitudinal study of 349 women with Vulvodynia was conducted. Participants completed online self-report measures of pain-related and sexual outcomes, depression, BEA, perceived injustice, and facets of PF (present-moment-awareness, pain acceptance, committed action) at baseline and after three months, overlapping with the COVID-19 pandemic.
Seventy per cent of women responded at both assessments (n=244). There were significant decreases in pain severity, pain-interference, present-moment-awareness, committed action, and a significant increase in depression at three-months. All the baseline psychosocial factors significantly correlated with at least one outcome at three-months. When adjusting for baseline outcome and demographics, committed action significantly positively predicted depression at three-months, and pain acceptance significantly positively predicted pain-interference at three-months.
Among women with Vulvodynia, pain acceptance and committed action are prospectively associated with pain-interference and depression. The reliability and generalisability of these results needs to be established given the overlap with the COVID-19 pandemic. Future studies should investigate whether targeting these factors enhances outcomes in Vulvodynia.
The mechanism for reduced pain sensitivity associated with Alzheimer's disease (AD) has not been illustrated. We hypothesize that amyloid beta 1-42 (Aβ1-42) in the spinal cord acts as an endogenous analgesic peptide to suppress pain induced by nerve injury.
We used chronic constriction injury of the sciatic nerve (CCI) to produce neuropathic pain in Sprague-Dawley rats. ELISA and immunohistochemistry were used to determine the level of Aβ1-42, the expression of Wnt3a/5b, and glial activation in the spinal cord. Western blotting was used to determine the expression of interleukins, the phosphorylation of NR2B and ERK1/2, and the nuclear accumulation of transcriptional factors YAP/TAZ. Thermal hyperalgesia and mechanical allodynia were assessed after CCI and pharmacological manipulations through intrathecal administration.
Nerve injury increases spinal level of Aβ1-42, while intrathecal administration of MK-8931 reduces the level of Aβ1-42 and facilitates mechanical allodynia. Intrathecal administration of Aβ1-42 suppresses pain behaviors in the early and late phases of neuropathy. Spinal administration of Aβ1-42 regulates the expression of interleukins, reducing glial activation and phosphorylation of NR2B and ERK1/2 in the spinal cord of CCI rats. Furthermore, intrathecal administration of Aβ1-42 decreases Wnt5b expression and suppresses the nuclear accumulation of YAP and TAZ. Blocking the interaction between Aβ1-42 and Frizzled receptors by cSP5 reverses the analgesic effects of Aβ1-42.
These findings suggest that spinal Aβ1-42 acts as an endogenous analgesic peptide through regulating cytokines and Wnt pathways. This study may provide a potential target for the development of novel analgesic peptides.
Pain related to temporomandibular disorders (TMD) can be linked with multiple site pain (MSP), and may associate with increased pain sensitivity, more frequently among women than men. The aim of the study was to examine the associations of pressure pain threshold (PPT) and tolerance (PPTo) with TMD and associated MSP in the Northern Finland Birth Cohort 1966 (NFBC1966) study.
Altogether 1961 NFBC1966 subjects attended clinical medical and dental examination at the Institute of Dentistry, University of Oulu in 2012-2013. Clinical examinations were carried out using a modified Diagnostic Criteria for TMD protocol (DC/TMD). MSP was defined based on questions regarding body pain sites. Additionally, PPT and PPTo were assessed using algometer measurements. Mann-Whitney U-test and Tobit regression models were used to analyze associations between TMD sub-diagnoses, MSP, PPT, and PPTo, stratified by sex. Further models were adjusted with anxiety and depressive symptoms, which were assessed using Hopkins Symptom Checklist-25 (HSCL-25) and two-way interaction terms.
Among females, lower PPT and PPTo associated with myalgia and arthralgia. Among males, lower PPT and PPTo associated with MSP-linked TMD. Tobit regression analysis showed significantly lower PPT and PPTo values in the myalgia and arthralgia subgroups among female TMD subjects. Among females, disc displacement with reduction had an inverse association with PPT and PPTo. Among males, lower PPTo associated with degenerative joint disease and MSP-linked TMD.
The pain regulatory mechanisms behind TMD act differently between the sexes as local TMD among females and MSP-linked TMD among males associated with pain sensitivity.
The objective of this systematic review was to investigate the effectiveness of electrical stimulation (ES) for neck pain (NP).
The databases CINAHL, Embase, MEDLINE (via OVID), PEDro and Web of Science were searched, with no date restrictions. Two independent reviewers selected randomized controlled trials (RCTs) reporting pain, range of motion or psychosocial factors in people with NP, in which ES was applied. Methodological quality was assessed using the PEDro scale. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to evaluate the quality of evidence. Thirty studies met eligibility criteria.
Main results showed evidence of moderate quality that ES combined with other intervention significantly decreases the pain intensity compared to other intervention immediately post-treatment and at short-term follow-up; evidence of low quality showed significant effects of ES combined with other intervention in decreasing neck disability compared to other intervention immediately post-treatment; evidence of very-low quality that ES increased the pressure pain threshold compared to placebo immediately post-treatment and that ES + other intervention also increased the pressure pain threshold compared to other intervention at short-term follow-up.
ES combined with other intervention seems to be useful to relieve pain and to improve disability in people with NP, however more studies are needed.
Exposure to stressful experiences is often accompanied by suppressing pain perception, referred to as stress-induced analgesia. The neuropeptides orexins are essential in regulating the mechanism that responds to stressful and painful stimuli. Meanwhile, the ventral tegmental area (VTA), as a part of descending pain inhibitory system, responds to noxious stimuli. The present study aimed to investigate the role of intra-VTA administration of orexin receptor antagonists on stress-induced antinociceptive responses in the animal model of acute pain.
Ninety-three adult Wistar rats weighing 230–250 g were unilaterally implanted by a cannulae above the VTA. Animals were pretreated with different doses (1, 3, 10, and 30 nM/0.3 μl) of SB334867 as the orexin-1 receptor antagonist and TCS OX2 29 as the orexin-2 receptor antagonist into the VTA, just 5 min before 6 min exposure to forced swim stress (FSS). Nociceptive threshold was measured using the tail-flick test as a model of acute pain.
The results showed that exposure to FSS could significantly increase analgesic responses. Moreover, intra-VTA administration of SB334768 and TCS OX2 29 blocked the antinociceptive effect of FSS in the tail-flick test.
The findings suggest that OX1 and OX2 receptors in the VTA might modulate the antinociceptive behaviors induced by FSS in part.
Neuropathic pain arises as a direct consequence of a lesion or disease affecting the somatosensory system. A number of preclinical studies have provided evidence for the involvement of cytokines, predominantly secreted by a variety of immune cells and by glial cells from the nervous system, in neuropathic pain conditions. Clinical trials and use of anti-cytokine drugs in different neuropathic etiologies support the relevance of cytokines as treatment targets. However, the use of such drugs, in particularly biotherapies, can provoke notable adverse effects. Moreover, it is challenging to select one given cytokine as target, among the various neuropathic pain conditions. It could thus be of interest to target other proteins, such as growth factors, in order to act more widely on the neuroinflammation network. Thus, platelet-rich plasma (PRP), an autologous blood concentrate, is known to contain a natural concentration of growth factors and immune system messengers and is widely used in the clinical setting for tissue regeneration and repair. In the present review, we critically assess the current knowledge on cytokines in neuropathic pain by taking into consideration both human studies and animal models. This analysis of the literature highlights the pathophysiological importance of cytokines. We particularly highlight the concept of time- and tissue- dependent cytokine activation during neuropathic pain conditions. Thus, direct or indirect cytokines modulation with biotherapies or growth factors appears relevant. In addition, we discuss therapeutic potential of localized injection of PRP as neuropathic pain treatment by pointing out the possible link between cytokines and the action of PRP.
The mechanisms underlying chronic phantom limb pain (PLP) are complex and insufficiently understood. Altered sensory thresholds are often associated with chronic pain but quantitative sensory testing (QST) in PLP has so far been inconclusive due to large methodological variation between studies and small sample sizes. In this study, we applied QST in 37 unilateral upper-limb amputees (23 with, 14 without PLP) and 19 healthy controls. We assessed heat pain (HPT), pressure pain (PPT), warmth detection (WDT), and two-point discrimination thresholds at the residual limb, a homologous point and the thenar of the intact limb as well as both corners of the mouth. We did not find significant differences in any of the thresholds between the groups. However, PLP intensity was negatively associated with HPT at all measured body sites except for the residual limb, indicating lower pain thresholds with higher PLP levels. Correlations between HPT and PLP were strongest in the contralateral face (r = -0.65, p < 0.001). Facial HPT were specifically associated with PLP, independent of residual limb pain (RLP) and various other covariates. HPT at the residual limb, however, were significantly associated with RLP, but not with PLP. We conclude that the association between PLP and, especially facial, HPT could be related to central mechanisms.
Women with Vulvodynia experience pain, related impacts on sex and daily functioning, and depression. While psychosocial factors are associated with outcomes in Vulvodynia, longitudinal data are limited, especially in mixed/spontaneous Vulvodynia. Broad psychological models such as Psychological Flexibility (PF) and content-specific factors such as body-exposure anxiety and avoidance during sexual activities (BEA), and perceived injustice, have not been adequately investigated in Vulvodynia. The aim of this study was to explore whether these factors assessed at baseline predict pain severity, pain-interference, sexual functioning and satisfaction, and depression three months later.
A longitudinal study of 349 women with Vulvodynia was conducted. Participants completed online self-report measures of pain-related and sexual outcomes, depression, BEA, perceived injustice, and facets of PF (present-moment-awareness, pain acceptance, committed action) at baseline and after three months, overlapping with the COVID-19 pandemic.
Seventy per cent of women responded at both assessments (n=244). There were significant decreases in pain severity, pain-interference, present-moment-awareness, committed action, and a significant increase in depression at three-months. All the baseline psychosocial factors significantly correlated with at least one outcome at three-months. When adjusting for baseline outcome and demographics, committed action significantly positively predicted depression at three-months, and pain acceptance significantly positively predicted pain-interference at three-months.
Among women with Vulvodynia, pain acceptance and committed action are prospectively associated with pain-interference and depression. The reliability and generalisability of these results needs to be established given the overlap with the COVID-19 pandemic. Future studies should investigate whether targeting these factors enhances outcomes in Vulvodynia.
The mechanism for reduced pain sensitivity associated with Alzheimer's disease (AD) has not been illustrated. We hypothesize that amyloid beta 1-42 (Aβ1-42) in the spinal cord acts as an endogenous analgesic peptide to suppress pain induced by nerve injury.
We used chronic constriction injury of the sciatic nerve (CCI) to produce neuropathic pain in Sprague-Dawley rats. ELISA and immunohistochemistry were used to determine the level of Aβ1-42, the expression of Wnt3a/5b, and glial activation in the spinal cord. Western blotting was used to determine the expression of interleukins, the phosphorylation of NR2B and ERK1/2, and the nuclear accumulation of transcriptional factors YAP/TAZ. Thermal hyperalgesia and mechanical allodynia were assessed after CCI and pharmacological manipulations through intrathecal administration.
Nerve injury increases spinal level of Aβ1-42, while intrathecal administration of MK-8931 reduces the level of Aβ1-42 and facilitates mechanical allodynia. Intrathecal administration of Aβ1-42 suppresses pain behaviors in the early and late phases of neuropathy. Spinal administration of Aβ1-42 regulates the expression of interleukins, reducing glial activation and phosphorylation of NR2B and ERK1/2 in the spinal cord of CCI rats. Furthermore, intrathecal administration of Aβ1-42 decreases Wnt5b expression and suppresses the nuclear accumulation of YAP and TAZ. Blocking the interaction between Aβ1-42 and Frizzled receptors by cSP5 reverses the analgesic effects of Aβ1-42.
These findings suggest that spinal Aβ1-42 acts as an endogenous analgesic peptide through regulating cytokines and Wnt pathways. This study may provide a potential target for the development of novel analgesic peptides.
Pain related to temporomandibular disorders (TMD) can be linked with multiple site pain (MSP), and may associate with increased pain sensitivity, more frequently among women than men. The aim of the study was to examine the associations of pressure pain threshold (PPT) and tolerance (PPTo) with TMD and associated MSP in the Northern Finland Birth Cohort 1966 (NFBC1966) study.
Altogether 1961 NFBC1966 subjects attended clinical medical and dental examination at the Institute of Dentistry, University of Oulu in 2012-2013. Clinical examinations were carried out using a modified Diagnostic Criteria for TMD protocol (DC/TMD). MSP was defined based on questions regarding body pain sites. Additionally, PPT and PPTo were assessed using algometer measurements. Mann-Whitney U-test and Tobit regression models were used to analyze associations between TMD sub-diagnoses, MSP, PPT, and PPTo, stratified by sex. Further models were adjusted with anxiety and depressive symptoms, which were assessed using Hopkins Symptom Checklist-25 (HSCL-25) and two-way interaction terms.
Among females, lower PPT and PPTo associated with myalgia and arthralgia. Among males, lower PPT and PPTo associated with MSP-linked TMD. Tobit regression analysis showed significantly lower PPT and PPTo values in the myalgia and arthralgia subgroups among female TMD subjects. Among females, disc displacement with reduction had an inverse association with PPT and PPTo. Among males, lower PPTo associated with degenerative joint disease and MSP-linked TMD.
The pain regulatory mechanisms behind TMD act differently between the sexes as local TMD among females and MSP-linked TMD among males associated with pain sensitivity.
The objective of this systematic review was to investigate the effectiveness of electrical stimulation (ES) for neck pain (NP).
The databases CINAHL, Embase, MEDLINE (via OVID), PEDro and Web of Science were searched, with no date restrictions. Two independent reviewers selected randomized controlled trials (RCTs) reporting pain, range of motion or psychosocial factors in people with NP, in which ES was applied. Methodological quality was assessed using the PEDro scale. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to evaluate the quality of evidence. Thirty studies met eligibility criteria.
Main results showed evidence of moderate quality that ES combined with other intervention significantly decreases the pain intensity compared to other intervention immediately post-treatment and at short-term follow-up; evidence of low quality showed significant effects of ES combined with other intervention in decreasing neck disability compared to other intervention immediately post-treatment; evidence of very-low quality that ES increased the pressure pain threshold compared to placebo immediately post-treatment and that ES + other intervention also increased the pressure pain threshold compared to other intervention at short-term follow-up.
ES combined with other intervention seems to be useful to relieve pain and to improve disability in people with NP, however more studies are needed.
Exposure to stressful experiences is often accompanied by suppressing pain perception, referred to as stress-induced analgesia. The neuropeptides orexins are essential in regulating the mechanism that responds to stressful and painful stimuli. Meanwhile, the ventral tegmental area (VTA), as a part of descending pain inhibitory system, responds to noxious stimuli. The present study aimed to investigate the role of intra-VTA administration of orexin receptor antagonists on stress-induced antinociceptive responses in the animal model of acute pain.
Ninety-three adult Wistar rats weighing 230–250 g were unilaterally implanted by a cannulae above the VTA. Animals were pretreated with different doses (1, 3, 10, and 30 nM/0.3 μl) of SB334867 as the orexin-1 receptor antagonist and TCS OX2 29 as the orexin-2 receptor antagonist into the VTA, just 5 min before 6 min exposure to forced swim stress (FSS). Nociceptive threshold was measured using the tail-flick test as a model of acute pain.
The results showed that exposure to FSS could significantly increase analgesic responses. Moreover, intra-VTA administration of SB334768 and TCS OX2 29 blocked the antinociceptive effect of FSS in the tail-flick test.
The findings suggest that OX1 and OX2 receptors in the VTA might modulate the antinociceptive behaviors induced by FSS in part.
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Jason M. Beneciuk, Lindsey Brown-Taylor, Faris Alodaibi, Stephen Kareha, Rett Holmes, Julie Fritz
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Ron Clijsen, Rahel Stoop, Erich Hohenauer, Dirk Aerenhouts, Peter Clarys, Carlina Deflorin, Jan Taeymans
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Jason M. Beneciuk, Lindsey Brown-Taylor, Faris Alodaibi, Stephen Kareha, Rett Holmes, Julie Fritz
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Ron Clijsen, Rahel Stoop, Erich Hohenauer, Dirk Aerenhouts, Peter Clarys, Carlina Deflorin, Jan Taeymans
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Jason M. Beneciuk, Lindsey Brown-Taylor, Faris Alodaibi, Stephen Kareha, Rett Holmes, Julie Fritz
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Ron Clijsen, Rahel Stoop, Erich Hohenauer, Dirk Aerenhouts, Peter Clarys, Carlina Deflorin, Jan Taeymans
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Jason M. Beneciuk, Lindsey Brown-Taylor, Faris Alodaibi, Stephen Kareha, Rett Holmes, Julie Fritz
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Ron Clijsen, Rahel Stoop, Erich Hohenauer, Dirk Aerenhouts, Peter Clarys, Carlina Deflorin, Jan Taeymans
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Jason M. Beneciuk, Lindsey Brown-Taylor, Faris Alodaibi, Stephen Kareha, Rett Holmes, Julie Fritz
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Ron Clijsen, Rahel Stoop, Erich Hohenauer, Dirk Aerenhouts, Peter Clarys, Carlina Deflorin, Jan Taeymans
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Jason M. Beneciuk, Lindsey Brown-Taylor, Faris Alodaibi, Stephen Kareha, Rett Holmes, Julie Fritz
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Ron Clijsen, Rahel Stoop, Erich Hohenauer, Dirk Aerenhouts, Peter Clarys, Carlina Deflorin, Jan Taeymans
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Jason M. Beneciuk, Lindsey Brown-Taylor, Faris Alodaibi, Stephen Kareha, Rett Holmes, Julie Fritz
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Ron Clijsen, Rahel Stoop, Erich Hohenauer, Dirk Aerenhouts, Peter Clarys, Carlina Deflorin, Jan Taeymans
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Jason M. Beneciuk, Lindsey Brown-Taylor, Faris Alodaibi, Stephen Kareha, Rett Holmes, Julie Fritz
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Ron Clijsen, Rahel Stoop, Erich Hohenauer, Dirk Aerenhouts, Peter Clarys, Carlina Deflorin, Jan Taeymans
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Jason M. Beneciuk, Lindsey Brown-Taylor, Faris Alodaibi, Stephen Kareha, Rett Holmes, Julie Fritz
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Ron Clijsen, Rahel Stoop, Erich Hohenauer, Dirk Aerenhouts, Peter Clarys, Carlina Deflorin, Jan Taeymans
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Jason M. Beneciuk, Lindsey Brown-Taylor, Faris Alodaibi, Stephen Kareha, Rett Holmes, Julie Fritz
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Ron Clijsen, Rahel Stoop, Erich Hohenauer, Dirk Aerenhouts, Peter Clarys, Carlina Deflorin, Jan Taeymans
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Jason M. Beneciuk, Lindsey Brown-Taylor, Faris Alodaibi, Stephen Kareha, Rett Holmes, Julie Fritz
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Ron Clijsen, Rahel Stoop, Erich Hohenauer, Dirk Aerenhouts, Peter Clarys, Carlina Deflorin, Jan Taeymans
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Jason M. Beneciuk, Lindsey Brown-Taylor, Faris Alodaibi, Stephen Kareha, Rett Holmes, Julie Fritz
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Ron Clijsen, Rahel Stoop, Erich Hohenauer, Dirk Aerenhouts, Peter Clarys, Carlina Deflorin, Jan Taeymans
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Jason M. Beneciuk, Lindsey Brown-Taylor, Faris Alodaibi, Stephen Kareha, Rett Holmes, Julie Fritz
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Ron Clijsen, Rahel Stoop, Erich Hohenauer, Dirk Aerenhouts, Peter Clarys, Carlina Deflorin, Jan Taeymans
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Jason M. Beneciuk, Lindsey Brown-Taylor, Faris Alodaibi, Stephen Kareha, Rett Holmes, Julie Fritz
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Ron Clijsen, Rahel Stoop, Erich Hohenauer, Dirk Aerenhouts, Peter Clarys, Carlina Deflorin, Jan Taeymans
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Jason M. Beneciuk, Lindsey Brown-Taylor, Faris Alodaibi, Stephen Kareha, Rett Holmes, Julie Fritz
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Ron Clijsen, Rahel Stoop, Erich Hohenauer, Dirk Aerenhouts, Peter Clarys, Carlina Deflorin, Jan Taeymans
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Jason M. Beneciuk, Lindsey Brown-Taylor, Faris Alodaibi, Stephen Kareha, Rett Holmes, Julie Fritz
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Ron Clijsen, Rahel Stoop, Erich Hohenauer, Dirk Aerenhouts, Peter Clarys, Carlina Deflorin, Jan Taeymans
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Jason M. Beneciuk, Lindsey Brown-Taylor, Faris Alodaibi, Stephen Kareha, Rett Holmes, Julie Fritz
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Ron Clijsen, Rahel Stoop, Erich Hohenauer, Dirk Aerenhouts, Peter Clarys, Carlina Deflorin, Jan Taeymans
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Jason M. Beneciuk, Lindsey Brown-Taylor, Faris Alodaibi, Stephen Kareha, Rett Holmes, Julie Fritz
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Ron Clijsen, Rahel Stoop, Erich Hohenauer, Dirk Aerenhouts, Peter Clarys, Carlina Deflorin, Jan Taeymans
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Jason M. Beneciuk, Lindsey Brown-Taylor, Faris Alodaibi, Stephen Kareha, Rett Holmes, Julie Fritz
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Ron Clijsen, Rahel Stoop, Erich Hohenauer, Dirk Aerenhouts, Peter Clarys, Carlina Deflorin, Jan Taeymans
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Jason M. Beneciuk, Lindsey Brown-Taylor, Faris Alodaibi, Stephen Kareha, Rett Holmes, Julie Fritz
Publication date: Available online 18 July 2021
Source: Archives of Physical Medicine and Rehabilitation
Author(s): Ron Clijsen, Rahel Stoop, Erich Hohenauer, Dirk Aerenhouts, Peter Clarys, Carlina Deflorin, Jan Taeymans
Neuropathic pain negatively affects quality of life among people living with HIV (PLWH). This study examined the feasibility of conducting a full-scale randomized-controlled trial of online acceptance and commitment therapy (“ACT OPEN”) for neuropathic pain in PLWH.
Using a parallel-groups design, thirty-eight participants were randomized to ACT OPEN or a waitlist control (2:1). Participants completed standard self-report outcome measures at baseline, and two- and five-months post-randomization. Participants were aware of their allocation, but assessment was blinded.
Twenty-five participants were randomized to ACT OPEN and 13 to the control (of 133 referrals). ACT OPEN completion was 69% and two-month trial retention was 82%. Treatment credibility and satisfaction scores for ACT OPEN were comparable to scores reported in previous trials of cognitive-behavioural treatments for pain. Four adverse events were reported during the study, including one serious adverse event; all of these were unrelated to the research procedures. Small to moderate effects and 95% confidence intervals suggest that the true effect may favour ACT OPEN for improvements in pain intensity/interference and depression.
A full-scale RCT of online ACT for pain management in PLWH may be feasible with refinements to trial design to facilitate recruitment.
Research on pain management in people living with HIV has primarily focused on pharmacological treatments with limited success. This is the first study to show the potential feasibility of a psychological treatment based on acceptance and commitment therapy delivered online and tailored for pain management in people with HIV (“ACT OPEN”). ACT OPEN may be a promising treatment in this population and further evaluation in a full-scale randomized-controlled trial appears warranted.
Trial Registration: The trial was registered (clinicaltrials.gov; NCT03584412).
The way people respond to pain is based on psychological mechanisms, beliefs and expectations. Mindfulness meditation (MM) has been shown to regulate pain and mental suffering through different mechanisms such as positive reappraisal, attentional and emotional regulation. Yet, subjective experience and meaning of pain in connection with MM are still largely unexplored.
The present mixed-methods study combined an interpretative-phenomenological qualitative approach with an experimental thermal pain paradigm to explore and compare the meaning of experiencing pain in 32 novices who received short meditation training and 30 experts in meditation practice (more than 10, 000 hr in life). We collected the qualitative data during in-depth semi-structured interviews where we probed participants’ response strategies. During the pain task, we collected self-reports of intensity and unpleasantness, while after the task we collected self-reports of avoidance, openness, vividness and blissfulness.
Five phenomenological clusters (PhC) emerged from the interviews, including three which described pain as an unpleasant sensation calling for: (1) experiential avoidance-suppression, (2) volitional agency-distanciation, or (3) a positive cognitive reappraisal and flexibility. Two additional clusters (4–5), containing mostly expert meditators, thematized pain sensation as an opportunity to gain metacognitive insights about mental processes, and to deconstruct one's suffering through these insights. PhC5 further integrates these insights with the recognition that suffering is part of the shared human experience and with the aspiration to relieve others from suffering. Each PhC was correlated to a unique profile of self-reports during the pain paradigm.
These findings need to be replicated in patients and practicing MM. They also warrant the integration of this mixed-method approach with brain imaging data to refine the experiential neuroscience of pain.
We compared the meaning of experiencing and regulating pain in novices and expert meditators using qualitative interviews. We identified five phenomenological clusters describing relevant features implicated in pain response strategies and meditation. These clusters were organized along a pseudo-gradient, which captured meditation expertise and predicted self-reports related to a pain paradigm and psychometric scales associated with pain and its regulation. These findings advance our understanding of the metacognitive mechanisms and beliefs underlying mindfulness meditation and can inform pain treatment strategies.
The nociceptive flexion reflex (NFR) is a spinally-mediated withdrawal reflex occurring in response to noxious stimuli and is used as an electrophysiological marker of spinal nociception. Although it is well-documented that the NFR is subject to powerful modulation of several personal factors, the effects of experimentally induced fatigue on the NFR have not yet been examined. Hence, this study aimed to characterize if and how fatigue affects spinal nociception in healthy adults.
The NFR of 58 healthy people was measured prior to and following rest and two fatiguing tasks performed in randomized order. The NFR was elicited by transcutaneous electrical stimulation of the sural nerve and objectified by electromyographic recordings from the biceps femoris muscle. An isokinetic fatiguing protocol was used to induce localized muscle fatigue of the hamstrings. The modified incongruent Stroop-word task was used to provoke mental fatigue. A linear mixed model analysis was performed to assess the influence of fatigue on the NFR.
Low-to-moderate levels experimentally induced localized muscle and mental fatigue did not affect the NFR in healthy adults. These results suggest that descending pain inhibitory processes to dampen spinal nociception are resistant to the effects of localized muscle and mental fatigue.
The relative robustness of the NFR to fatigue may be beneficial in both clinical and research settings where the influence of confounders complicates interpretation. Furthermore, the findings possibly help enhance our understanding on why even demanding cognitive/physical exercise-based treatment programs form effective treatment strategies for patients with chronic pain.
The present study unraveled that low-to-moderate levels experimentally induced localized muscle and mental fatigue did not affect the NFR. These results suggest that descending pain inhibitory processes to dampen spinal nociception are resistant to the effects of localized muscle and mental fatigue. This relative robustness of the NFR may be beneficial in a clinical setting in which the evaluation of spinal nociception that is unaffected by clinical symptoms of fatigue may be useful (e.g. chronic fatigue syndrome, cancer-related fatigue, etc.).
To evaluate if early improvements in pain and function with subcutaneous tanezumab are meaningful and sustained over 24 weeks.
Patients with moderate-to-severe osteoarthritis (hip or knee) in Europe and Japan were randomized to placebo, tanezumab 2.5 mg or tanezumab 5 mg (baseline, Week 8 and Week 16). Outcomes included: average daily index joint pain score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscales, rescue medication use, WOMAC responders (within-patient ≥30% reduction in WOMAC Pain or Physical Function), Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) responders (within-patient) and Patient-reported Treatment Impact Assessment-Modified questionnaire.
Patients received placebo (n = 282), tanezumab 2.5 mg (n = 283) or tanezumab 5 mg (n = 284). Changes from baseline in average daily index joint pain (within the first week) and WOMAC subscales (Week 2 through Week 24) were greater for each tanezumab group versus placebo (least squares [LS] mean, unadjusted p ≤ .05). Rescue medication use (days/week) was lower for each tanezumab group versus placebo from Week 2 through Week 12 (LS mean, unadjusted p ≤ .05) but not at Week 16 or 24. A higher proportion of each tanezumab group than placebo achieved ≥30% reduction from baseline in WOMAC Pain or Physical Function, or OMERACT-OARSI response (Week 2 through Week 24, unadjusted p ≤ .05), or were satisfied with treatment at Week 24 (unadjusted p ≤ .05).
Subcutaneous tanezumab, compared with placebo, reduced pain within the first week, and pain and function were improved throughout 24 weeks. The proportions of responders and patients satisfied were higher with tanezumab than placebo.
ClinicalTrials.gov:NCT02709486.
This exploratory analysis of data from a placebo-controlled, Phase 3 study of patients with moderate-to-severe osteoarthritis of the hip or knee for whom standard analgesics were not effective or could not be taken, found that onset of efficacy of subcutaneous tanezumab was within the first week, and efficacy was maintained through the 24-week treatment period. Tanezumab was effective in those patients with the most radiologically severe osteoarthritis.
Effective treatment of longstanding Complex Regional Pain Syndrome (CRPS) is a challenge, as causal mechanisms remain elusive. People with CRPS frequently report distorted subjective perceptions of their affected limb. Evidence of pain reduction when the affected limb is visually altered in size suggests that visual illusions used to target central processing could restore coherence of this disrupted limb representation. We hypothesized that using virtual reality that alters hand image to match the patient's desired hand appearance would improve body perception disturbance and pain. Also, repeated exposure would maintain any therapeutic effect.
A blinded randomized controlled trial of 45 participants with refractory upper-limb CRPS and body perception disturbance (BPD) viewed a digital image of their affected hand for 1 min. The image was digitally altered according to the patient's description of how they desired their hand to look in the experimental group and unaltered in the control group. BPD and pain were measured pre- and post-intervention. A subgroup was followed up 2 weeks after a course of repeated interventions.
BPD (mean-6, ±SD 7.9, p = 0.036, effect size [ES] = 0.6) and pain intensity (mean-0.43, ±SD 1.3, p = 0.047, ES = 0.5) reduced in 23 participants after single exposure compared to controls (n = 22). At follow-up, the subgroup (experimental n = 21; control n = 18) showed sustained pain reduction only (p = 0.037, ±SD 1.9, ES = 0.7), with an overall 1.2 decrease on an 11-point scale.
Visually changing the CRPS hand to a desired appearance modulates BPD and pain suggesting therapeutic potential for those with refractory CRPS. Further research to optimize this therapeutic effect is required.
Visual bodily illusions that change the shape and appearance of the painful CRPS hand to that desired by the patient result in a rapid amelioration of pain and body perception disturbance in people with longstanding CRPS. These findings highlight the future potential of this drug-free approach in the treatment of refractory CRPS.
Together, neck pain and back pain are the first cause of disability worldwide, accounting for more than 10% of the total years lived with disability. In this context, chiropractic care provides a safe and effective option for the management of a large proportion of these patients. Chiropractic is a healthcare profession mainly focused on the spine and the treatment of spinal disorders, including spine pain. Basic studies have examined the influence of chiropractic spinal manipulation (SM) on a variety of peripheral, spinal and supraspinal mechanisms involved in spine pain. While spinal cord mechanisms of pain inhibition contribute at least partly to the pain-relieving effects of chiropractic treatments, the evidence is weaker regarding peripheral and supraspinal mechanisms, which are important components of acute and chronic pain. This narrative review highlights the most relevant mechanisms of pain relief by SM and provides a perspective for future research on SM and spine pain, including the validation of placebo interventions that control for placebo effects and other non-specific effects that may be induced by SM.
Spinal manipulation inhibits back and neck pain partly through spinal segmental mechanisms and potentially through peripheral mechanisms regulating inflammatory responses. Other mechanisms remain to be clarified. Controls and placebo interventions need to be improved in order to clarify the contribution of specific and non-specific effects to pain relief by spinal manipulative therapy.
Trigeminal neuralgia (TN) is a rare condition for which there are multiple treatment options available. To date, there has been difficulty in comparing the outcomes of treatment due to the variety of patient-reported outcome measures (PROMs) and their inadequate psychometric testing. The aim of this review was to assess the psychometric properties of PROMs used to date in TN and make recommendations for their use in future studies.
Five electronic databases (MEDLINE, EMBASE, CINAHL Plus, PsycINFO, Health and Psychosocial Instruments) were searched for studies assessing the development of PROMs or their psychometric properties in TN studies. The records obtained were assessed independently by two reviewers for their methodological quality, following guidance from the Consensus-based Standards for the selection of Health Measurement Instruments (COSMIN).
Six studies were identified and information on five PROMs (Brief Pain Inventory Facial (BPI-F), Visual Analogue Scale (VAS), Barrow Neurology Institute Pain Scale (BNI-PS), Penn Facial Pain Scale-Revised (Penn-FPS-R) and Trigeminal Neuralgia Quality of Life Score) were retrieved. The Penn-FPS-R demonstrated moderate quality evidence for sufficient content validity. The BPI-F showed moderate evidence for sufficient internal consistency and structural validity but low evidence for inconsistent content validity. The Trigeminal Neuralgia Quality of Life score showed very low-quality evidence for insufficient content validity, structure validity and responsiveness. No evidence was found on the assessment of any psychometric properties of the VAS and BNI-PS in TN.
There is limited evidence of the psychometric performance of patient-reported outcomes for TN and recommendations for their inclusion in future studies cannot be made. The validation of PROMs in TN studies should be a priority in this field of research.
This review highlights the knowledge gap in the field of psychometrics of patient reported outcomes measures in the field of TN. Given the unavailability of an objective outcome measure for pain or health related quality of life, psychometrically sound PROMs are essential for assessing medical and surgical treatment outcomes in TN.
As in other fields of medicine, development of new medications for management of neuropathic pain has been difficult since preclinical rodent models do not necessarily translate to the clinics. Aside from ongoing pain with burning or shock-like qualities, neuropathic pain is often characterized by pain hypersensitivity (hyperalgesia and allodynia), most often towards mechanical stimuli, reflecting sensitization of neural transmission.
We therefore performed a systematic literature review (PubMed-Medline, Cochrane, WoS, ClinicalTrials) and semi-quantitative meta-analysis of human pain models that aim to induce central sensitization, and generate hyperalgesia surrounding a real or simulated injury.
From an initial set of 1569 reports, we identified and analysed 269 studies using more than a dozen human models of sensitization. Five of these models (intradermal or topical capsaicin, low- or high-frequency electrical stimulation, thermode-induced heat-injury) were found to reliably induce secondary hyperalgesia to pinprick and have been implemented in multiple laboratories. The ability of these models to induce dynamic mechanical allodynia was however substantially lower. The proportion of subjects who developed hypersensitivity was rarely provided, giving rise to significant reporting bias. In four of these models pharmacological profiles allowed to verify similarity to some clinical conditions, and therefore may inform basic research for new drug development.
While there is no single “optimal” model of central sensitization, the range of validated and easy-to-use procedures in humans should be able to inform preclinical researchers on helpful potential biomarkers, thereby narrowing the translation gap between basic and clinical data.
Being able to mimic aspects of pathological pain directly in humans has a huge potential to understand pathophysiology and provide animal research with translatable biomarkers for drug development. One group of human surrogate models has proven to have excellent predictive validity: they respond to clinically active medications and do not respond to clinically inactive medications, including some that worked in animals but failed in the clinics. They should therefore inform basic research for new drug development.
This study aims to evaluate the efficacy of 10-kHz high-frequency (HF10) devices as a rescue treatment in patients with failure of conventional spinal cord stimulation (SCS) therapy for chronic pain without the need to change the spinal hardware.
In this real-world prospective study, patients with neuropathic pain treated with conventional tonic SCS in whom the therapy had failed, either during the trial phase or after a period of optimal functioning, were recruited throughout 2 years for HF10-SCS therapy. Data on analgesia, functionality, analgesics use and treatment safety were collected 12 months after treatment.
Eleven of the 18 (61%) patients included in the study were successfully rescued with HF10-SCS. Of them, 5 out of 12 (45%) were in the trial phase and six out of six (100%) had previously functioning implants. A significant improvement in low-back and limb pain was obtained (p = 0.003 and p = 0.0001, respectively). Treatment success was significantly associated with gender (p = 0.037), weight (p = 0.014), body mass index (BMI) (p = 0.007) and time of rescue (p = 0.015). A linear regression test confirmed a significant association between treatment failure and BMI and gender (p = 0.004).
Our results suggest that analgesic rescue with HF10-SCS is an effective therapeutic option for non-responders to conventional SCS, although obesity might be a limiting factor for treatment success. Nevertheless, more comprehensive studies are needed to corroborate our findings.
This study shows that high-frequency stimulation may be useful in patients with failure of conventional tonic stimulation for chronic pain, both in the trial phase and in previously implanted subjects. The novelty of this study lies in the use of the implanted epidural electrodes, which avoids the need for further surgery. The results in terms of pain control and recovery of functionality are satisfactory. In addition, variables such as male gender and high body mass index could be predictors of therapy failure.
Guidelines recommend self-management for most people living with persistent musculoskeletal low back pain (PMLBP) when surgery is ruled out. Conveying this message to patients can be challenging. This study examined patients' perceptions of reassuring communications from surgical spine team practitioners attempting to deliver this message in a single consultation.
Pre-consultation baseline measures included levels of pain, disability and previous consultation history. Patients' perceptions of reassuring communications were measured within 1-week post-consultation. The outcome variables, measured at 3-month follow-up, included patients’ report of subsequent GP visits for back pain, the number of other healthcare providers consulted for back pain and distress.
Data from 296 patients (9.8% loss to follow-up) were analysed using hierarchical regression models, controlling for demographic, clinical and study-related factors. In each model, perceived reassurance accounted for a small but significant variance, above and beyond other predictors. Further GP visits were predicted by disability at baseline and perceived reassurance (adjusted R2 of 14.6%). Subsequent consultations with any healthcare professionals were predicted by a shorter duration of back pain, disability at baseline and perceived reassurance (adj. R2 = 10.6%). Distress was predicted by older age, disability and reassurance (adj. R2 = 59.5%).
Findings suggest that better communication in consultations with orthopaedic spine clinicians might help reduce unnecessary subsequent healthcare utilization and distress.
Low back pain patients' perceptions of their communication with orthopaedic spine practitioners are associated with subsequent healthcare seeking and distress at follow-up. This study examines the intersection of two important but fairly neglected areas in the pain research: provider communication and patient healthcare utilization.
Chronic pain in children is a serious issue, therefore calling for effective prevention/intervention measures. This study aimed to evaluate the efficacy of an educational movie on pain knowledge in school children in general and on pain-related behaviours and pain intensity in those who are affected by chronic pain. Regarding those affected, the association between pain knowledge and intensity, as well as the potential mediating effect of pain-related behaviours, were investigated.
Recruited from four schools, N = 381 students (51.7% female; M age = 11.4, SD = 0.95) participated, of which n = 108 reported chronic pain. Each school was randomly allocated to the intervention or control group (cluster-randomization). At two time points spaced 4–5 weeks apart, students provided information on their pain knowledge, pain-related behaviour (passive pain coping, pain-related disability, missed school days, medication use) and pain intensity. After the first assessment, students in the intervention group watched an educational movie. Multilevel linear models for all outcomes were calculated as well as a mediation analysis.
Pain knowledge increased significantly in the intervention group (β = 2.76 [95% CI 2.20, 3.31]). However, no significant time-by-group interactions were found for pain-related behaviour or pain intensity. The mediation model identified that the indirect effect of pain knowledge on pain intensity was mediated by pain-related behaviour (β = −0.18, p = 0.014 and β = 0.38, p < 0.001, respectively).
Educational movies may be an effective tool for educating students about pain management. However, the knowledge gained may not be sufficient to improve pain behaviour and intensity overall.
A 10-min educational movie on chronic pain management was tested in school children (N = 381). Following the intervention, knowledge of chronic pain concepts was statistically greater in the intervention group compared to the control group not watching the movie. Furthermore, a mediation model theoretically determined whether an association between pain knowledge and pain intensity exists, and whether this is explained by level of dysfunctional pain-related behaviorisms. Full mediation was confirmed.
In recent years, the delivery of health services has undergone a major paradigm shift towards expanded outpatient services and widespread use of telemedicine. Post-herpetic neuralgia (PHN) is a treatment recalcitrant neuropathic pain condition referring to pain persisting more than three months from the initial onset of an acute herpes zoster. QUTENZA® (capsaicin 8% patch) is a single 1-hr localized treatment for PHN and can provide several months of pain relief per application. However, patient access to capsaicin 8% patch is limited due to sensitive handling protocols that require the patch application to occur under physicians or healthcare professionals under the close supervision of a physician. Herein, we describe a successful treatment of PHN at-home, using capsaicin 8% patch, performed under full supervision and instruction from a physician using video telehealth services.
This is a case report of the successful treatment of post-herpetic neuralgia at-home using Capsaicin 8% patch. The procedure was performed under full supervision and instruction from a physician using video telehealth services. Not only did the patient tolerate the procedure and have significant efficacy, she voiced preference to repeat treatment in this manner versus going back to the office.
While pain is common in older adults, the association with physical activity remains unclear. Currently, the role physical activity plays in impacting pain developing over time is not well defined.
Latent transition analysis (LTA) is a model-based approach to identifying underlying subgroups in a population, longitudinally, based on measured characteristics. In this study, LTA was used to explore the associations between physical activity levels and pain classes of adults aged over 50 years, from the Irish Longitudinal Study on Ageing (n = 8,175) across three waves of data collection (4 years).
Using three previously established pain classes (No Pain; Low–Moderate Impact Pain; High Impact Pain), 66% of older adults were classified as having ‘No Pain’ across the three waves. At Wave 1, individuals reporting low (OR = 4.00, 95% CI [3.21, 5.17]) or moderate (OR = 1.59, 95% CI [1.27, 1.99]) levels of physical activity are more likely to be in the High Impact Pain class, than the No Pain class. Longitudinally, individuals in the No Pain class with low or moderate physical activity were more likely to transition to the High Impact Pain class compared to those with higher physical activity scores (from Wave 1 to Wave 2, OR = 1.90, 95% CI [1.15, 3.37]; and from Wave 2 to Wave 3, OR = 2.27, 95% CI [1.40, 4.74]).
Older adults who do not meet minimum physical activity guidelines for moderate intensity exercise are at increased risk of higher impact pain when followed over 4 years.
Older adults who do not meet minimum physical activity guidelines are at increased risk of transitioning to higher impact pain classes when followed over 4 years.
