The role of peripheral vasopressin 1A and oxytocin receptors on the subcutaneous vasopressin antinociceptive effects

Abstract

Background

Vasopressin (AVP) seems to play a role as an antinociceptive neurohormone, but little is known about the peripheral site of action of its antinociceptive effects. Moreover, AVP can produce motor impairment that could be confused with behavioural antinociception. Finally, it is not clear which receptor is involved in the peripheral antinociceptive AVP effects.

Methods

In anaesthetized rats with end-tidal CO₂ monitoring, extracellular unitary recordings were performed, measuring the evoked activity mediated by Aβ-, Aδ-, C-fibres and post-discharge. Behavioural nociception and motor impairment were evaluated under subcutaneous AVP (0.1–10 μg) using formalin and rotarod tests. Selective antagonists to vasopressin (V_1AR) or oxytocin receptors (OTR) were used. Additionally, vasopressin and oxytocin receptors were explored immunohistochemically in skin tissues.

Results

Subcutaneous AVP (1 and 10 μg/paw) induced antinociception and a transitory reduction of the end-tidal CO₂. The neuronal activity associated with Aδ- and C-fibre activation was diminished, but no effect was observed on Aβ-fibres. AVP also reduced paw flinches in the formalin test and a transitory locomotor impairment was also found. The AVP-induced antinociception was blocked by the selective antagonist to V_1AR (SR49059) or OTR (L368,899). Immunohistochemical evidence of skin VP and OT receptors is given.

Conclusions

Subcutaneous AVP produces antinociception and behavioural analgesia. Both V1a and OTR participate in those effects. Our findings suggest that antinociception could be produced in a local manner using a novel vasopressin receptor located in cutaneous sensorial fibres. Additionally, subcutaneous AVP also produces important systemic effects such as respiratory and locomotor impairment.

Significance

Our findings support that AVP produces peripheral antinociception and behavioural analgesia in a local manner; nevertheless, systemic effects are also presented. Additionally, this is the first detailed electrophysiological analysis of AVP antinociceptive action after subcutaneous administration. The results are reasonably explained by the demonstration of V_1AR and OTR in cutaneous fibres.

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The contribution of pain in determining the health status of cancer patients with bone metastases: A secondary analysis of data from three Phase III registration trials

Abstract

Background

We aimed to provide a simple, descriptive health-status profile for cancer patients with bone metastases, based on the EuroQol EQ-5D, a tool commonly used to measure health utility scores, and to evaluate its association with the Brief Pain Inventory (BPI), a legacy pain-assessment tool. Although pain is one of five health-status dimensions measured by the EQ-5D, our understanding of how pain relates to the other EQ-5D dimensions is limited.

Methods

We derived data from 5500 patients with bone metastases who completed the EQ-5D and BPI. Regression analyses examined how BPI severity and interference scores correlated with EQ-5D utility scores and how BPI items associated with EQ-5D items, for the entire sample and by disease-type subgroup.

Results

Regardless of cancer site, the percentage of patients reporting moderate/severe problems in each of the five EQ-5D dimensions were pain/discomfort, 78%; usual activities, 58%; mobility, 55%; anxiety/depression, 57%; and self-care, 26%. BPI pain interference explained more of the variability in the EQ-5D utility scores than did pain severity (R² = 41% vs. 34%). BPI worst pain, average pain, pain now, interference with general activity, and interference with work significantly predicted EQ-5D pain/discomfort, with odds ratio estimates <1.

Conclusions

Pain/discomfort was the worst-rated dimension of the EQ-5D in this population, but the relationship of this item to BPI pain severity was modest, suggesting that the single pain item of the EQ-5D may be of limited utility in studies for which pain is an endpoint.

Significance

Health-status dimensions include more than pain. We examine the contribution of pain severity and pain-related functional interference in determining the health status of cancer patients with bone metastases. The pain dimension from a health-status measure may be an inadequate metric in clinical trials/clinical practice when pain is an important outcome.

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Changing the size of a mirror-reflected hand does not affect pain perception: A repeated measures study on healthy human participants

Abstract

Background

Studies suggest that observing magnified and minified body parts using mirrors, lenses and virtual reality may affect pain perception. However, the direction of effect varies between studies. The aim of the present study was to evaluate the effect of observing a normal-sized, magnified and minified reflection of a hand on perceptual embodiment and contact-heat stimuli.

Methods

Participants (n = 46) observed a normal-sized, magnified and minified reflection of the hand and a no-reflection condition while performing synchronized finger movements for 3 min (adaptive phase). Measurements of embodiment were taken before adaptive phase, pre- and post-contact-heat stimuli.

Results

There were no differences in pain threshold nor tolerance between reflection and no-reflection conditions. Altering the size of the reflection of the hand did not affect estimates of pain threshold nor tolerance. The temperature for warm detection threshold was lower when participants were observing the magnified reflection of the hand compared with the no-reflection condition. Perceptual embodiment of the reflection of the hand was stronger after an adaptive phase with visuo-motor feedback, and the painful stimuli did not weaken the perceptual experience.

Conclusion

Observing a reflection of the hand in front of a mirror did not alter heat pain threshold nor tolerance when compared with a no-reflection condition, and altering the size of the reflection did not affect pain perception. Researchers and clinicians using visual feedback techniques may consider including an adaptive phase with visuo-motor feedback to facilitate embodiment of the viewed body part.

Significance

An adaptive phase with visuo-motor feedback enhances the perceptual experience of embodiment of a reflection of a hand and a painful stimulus does not weaken the experience. This should be considered when using visual feedback techniques for pain management.

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The effect of changes in pain expectations on persistent pain following a road traffic crash

Abstract

Background

Recovery expectations can influence outcomes after injury, but little is known about the course of expectations over time or factors predicting changes in expectations. This study aimed to describe how expectations of persistent pain change over time following a non-catastrophic injury sustained in a road traffic crash (RTC); identify the early predictors of change in expectations over time; and examine whether change in expectations predicted pain at 24 months post-RTC.

Methods

One hundred and seventy-seven participants (Mage = 49.25; SD = 14.15; 66.1% female) reported their expectations of persistent pain (1 = no risk that pain will become persistent, 10 = highest risk) at approximately 6, 12 and 24 months post-injury via survey. Measures of pain, emotional distress, post-traumatic stress, fear avoidance beliefs, social support and quality of life were also measured via survey at each time point.

Results

Cluster analysis revealed four clusters: 42% of participants showed a pattern of stable expectations (stable high-risk, n = 74), whereas 58% of participants showed changes in expectations over time (decreasing risk, n = 31; increasing risk, n = 44; risk peaking at 12 months, n = 28). Hierarchical linear regression models demonstrated that the clusters were a better statistical predictor of pain at 24 months than a single measure of expectation taken at 6 months post-injury. Pain, anxiety, depression and physical health-related quality of life at 6 months were associated with cluster affiliation.

Conclusions

Assessment of patterns of pain expectancy change is a superior means of determining long-term pain levels. Understanding expectancy change patterns will help provide more nuanced targets for pain intervention.

Significance

This study extends previous work by investigating persistent pain expectancies over time in a compensation-seeking cohort with non-catastrophic injuries. It identifies factors that are associated with changing expectations, providing targets for clinical intervention. The study shows that expectations can change over time. Conversations with patients about their expectations should be ongoing.

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Paeoniflorin attenuates postoperative pain by suppressing Matrix Metalloproteinase-9/2 in mice

Abstract

Background

Recent studies have implicated that matrix metalloproteinase (MMP)-9 and MMP-2 play key roles in neuropathic pain due to their facilitation of inflammatory cytokine maturation and induction of neuroinflammation. However, the role of MMP-9/2 in postoperative pain is still unclear. We previously suggested that the natural compound paeoniflorin inhibited microglia activation induced by morphine treatment. In the present study, we demonstrated that paeoniflorin could alleviate postoperative pain via specific inhibition of matrix metalloproteinases (MMPs).

Methods

Mice received a plantar incision surgery and their mechanical allodynia was assessed with von Frey filaments. The activity of MMP-9/2 was determined by gelatin zymography. Cell signalling was assayed by western blot and immunohistochemistry.

Results

The expression of MMP-9/2 was significantly increased in mice spinal cords with plantar incision surgery. Paeoniflorin remarkably suppressed the activity of MMP-9/2 and relieved plantar incision-induced mechanical allodynia. Interestingly, the administration of paeoniflorin blocked the maturation of interleukin-1β, which is a critical substrate of MMPs. Thereafter, paeoniflorin markedly suppressed microglia activation, inhibited the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and the expression of neuronal c-Fos.

Conclusion

These results indicated that MMP-9/2 activation in spinal microglia plays a key role in incision-induced mechanical allodynia in mice. Moreover, utilizing paeniflorin blockage of the microglia MMP-9/2 activity might represent a valuable alternative for treating postoperative pain.

Significance

Our results provided direct evidence for the first time that paeoniflorin can inhibit plantar incision-induced microglia TLR4/MMP-9/2/IL-1β signalling pathway and suppress postoperative pain. Thus, regulation of microglia MMP-9/2 may provide a new strategy for ameliorating postoperative pain.

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[Perspectives] Dengue

In 1780 Benjamin Rush—a physician and a founding father of the USA—noted the appearance of an alarming epidemic in his home city of Philadelphia. Rush was familiar with the intricate nosologies of fevers generated by his late-Enlightenment colleagues, but this outbreak had a distinctive symptom: “the pains which accompanied this fever were exquisitely severe in the head, back and limbs”. He deployed the usual purging, soothing, and strengthening remedies, but with little success, and he observed that “its general name among all classes of people was the break-bone fever”.

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Less Exercise and More Drugs: How a Low-Income Population Manages Chronic Pain

Ecological Momentary Assessment of Pain, Fatigue, Depressive, and Cognitive Symptoms Reveals Significant Daily Variability in Multiple Sclerosis

Pain, Fatigue, and Cognitive Symptoms Are Temporally Associated Within but Not Across Days in Multiple Sclerosis

How Do Pain, Fatigue, Depressive, and Cognitive Symptoms Relate to Well-Being and Social and Physical Functioning in the Daily Lives of Individuals With Multiple Sclerosis?

Development and Preliminary Psychometrics of the Exercise Therapy Burden Questionnaire for Patients With Chronic Conditions

Long-Term Deterioration of Perceived Health and Functioning in Adults With Cerebral Palsy

Preliminary Investigation of Pain-Related Changes in Cerebral Blood Volume in Patients With Phantom Limb Pain

Rehabilitation Services Use and Patient-Reported Outcomes Among Older Adults in the United States

Mindfulness Is Associated With Treatment Response From Nonpharmacologic Exercise Interventions in Knee Osteoarthritis

Observe to get pain relief: current evidence and potential mechanisms of socially learned pain modulation

No abstract available

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Defining chronic pain in epidemiological studies: a systematic review and meta-analysis

Abstract AbstractThe objective was to document the operational definitions applied in epidemiological studies of chronic pain and to examine whether pain definitions and other methodological factors are systematically related to prevalence estimates. MEDLINE, EMBASE, and PsychINFO were searched for original research reports with study samples of at least 1000 individuals, excluding studies of less than 5 out of 15 selected body regions and studies solely concerned with specific pain conditions. Meta-analyses and meta-regressions were applied with random effects models; covariates were geography, sampling year, survey method, sampling frame, participation rate, percentage women of all participants, pain duration, and pain location. Of 6791 hits, 86 studies were included in the syntheses. The phrasing, content, and combinations of the chronic pain definition criteria were highly inconsistent, with virtually no 2 studies from independent research groups using the exact same criteria. Prevalence estimates ranged from 8.7% to 64.4%, with a pooled mean of 31%. Huge heterogeneity was shown in all forest plots. Prevalence estimates were significantly related to survey method (β = −10.8 [95% confidence interval: −17.2 to −4.4]), but it only counted for a small fraction of the between-studies variation in the estimates. There were also interaction effect of survey method by sex (female–male prevalence ratio [95% confidence interval]: questionnaire = 1.20 [1.16 to 1.25], and interview = 1.38 [1.29 to 1.47]). The other covariates investigated were not significantly related to the prevalence estimates. Researchers and clinicians should be aware of the probability that interview survey method of collecting data may give lower chronic pain reporting than questionnaire survey method and that this effect may be stronger in men than women.

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Fully implantable, battery-free wireless optoelectronic devices for spinal optogenetics

Abstract AbstractThe advent of optogenetic tools has allowed unprecedented insights into the organization of neuronal networks. Although recently developed technologies have enabled implementation of optogenetics for studies of brain function in freely moving, untethered animals, wireless powering and device durability pose challenges in studies of spinal cord circuits where dynamic, multidimensional motions against hard and soft surrounding tissues can lead to device degradation. We demonstrate here a fully implantable optoelectronic device powered by near-field wireless communication technology, with a thin and flexible open architecture that provides excellent mechanical durability, robust sealing against biofluid penetration and fidelity in wireless activation, thereby allowing for long-term optical stimulation of the spinal cord without constraint on the natural behaviors of the animals. The system consists of a double-layer, rectangular-shaped magnetic coil antenna connected to a microscale inorganic light-emitting diode (μ-ILED) on a thin, flexible probe that can be implanted just above the dura of the mouse spinal cord for effective stimulation of light-sensitive proteins expressed in neurons in the dorsal horn. Wireless optogenetic activation of TRPV1-ChR2 afferents with spinal μ-ILEDs causes nocifensive behaviors and robust real-time place aversion with sustained operation in animals over periods of several weeks to months. The relatively low-cost electronics required for control of the systems, together with the biocompatibility and robust operation of these devices will allow broad application of optogenetics in future studies of spinal circuits, as well as various peripheral targets, in awake, freely moving and untethered animals, where existing approaches have limited utility.

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Peripheral oxytocin receptors inhibit the nociceptive input signal to spinal dorsal horn wide-dynamic-range neurons

Abstract AbstractOxytocin (OT) has emerged as a mediator of endogenous analgesia in behavioral and electrophysiological experiments. In fact, OT receptors (OTRs) in the spinal dorsal horn participate in a selective inhibition of the neuronal activity mediated by Aδ and C fibers but not Aβ fibers. This study shows that OTRs are expressed in the terminal nerve endings and are able to inhibit nociceptive neuronal firing. Indeed, local peripheral OT blocked the first sensorial activity of Aδ and C fibers recorded in the spinal cord neurons. Furthermore, using the formalin behavioral nociceptive test, we demonstrated that only ipsilateral OTR activation inhibits pain behavior. Our data are reinforced by the fact that the OTR protein is expressed in the sciatic nerve. Consistent with this, immunofluorescence of primary afferent fibers suggest that OTRs could be located in nociceptive-specific terminals of the skin. Taken together, our results suggest that OTRs could be found in nociceptive terminals and that on activation they are able to inhibit nociceptive input.

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Autonomic responses to tonic pain are more closely related to stimulus intensity than to pain intensity

Abstract AbstractPain serves the protection of the body by translating noxious stimulus information into a subjective percept and protective responses. Such protective responses rely on autonomic responses that allocate energy resources to protective functions. However, the precise relationship between objective stimulus intensity, subjective pain intensity, autonomic responses, and brain activity is not fully clear yet. Here, we addressed this question by continuously recording pain ratings, skin conductance, heart rate, and electroencephalography during tonic noxious heat stimulation of the hand in 39 healthy human subjects. The results confirmed that pain intensity dissociates from stimulus intensity during 10 minutes of noxious stimulation. Furthermore, skin conductance measures were significantly related to stimulus intensity but not to pain intensity. Correspondingly, skin conductance measures were significantly related to alpha and beta oscillations in contralateral sensorimotor cortex, which have been shown to encode stimulus intensity rather than pain intensity. No significant relationships were found between heart rate and stimulus intensity or pain intensity. The findings were consistent for stimulation of the left and the right hands. These results suggest that sympathetic autonomic responses to noxious stimuli in part directly result from nociceptive rather than from perceptual processes. Beyond, these observations support concepts of pain and emotions in which sensory, motor, and autonomic components are partially independent processes that together shape emotional and painful experiences.

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Day-to-day experience in resolution of pain after surgery

Abstract AbstractWe know little about the individual pain experience of patients recovering from surgery in the first weeks after hospital discharge. Here, we examine individual differences in the day-to-day experience after 2 major surgeries: lower limb total major joint arthroplasty (TJA) and cesarean delivery (CD). Fifty-five TJA patients and 157 CD patients were recruited to complete questionnaires and record their daily pain experiences after surgery. After hospital discharge, patients recorded their pain intensity once daily for 60 days (CD) or twice daily for 2 weeks, once daily for 2 weeks, weekly for 8 weeks, and monthly for 3 months (TJA). Pain scores were modeled using growth curve and Bayesian change-point models. Individual differences in the model fits were examined for evidence of day-to-day differences in pain. A log time model was the simplest model that fit the data, but examination of the residuals revealed high autocorrelation representing misspecification. A change-point model fit the data better and revealed that the form of recovery fundamentally changed between days 10 and 21 after surgery. These data add meaningfully to our understanding of recovery from pain after surgery by extending the period of frequent observations a few days after surgery to a 2-month period. These high time resolution data suggest that there is a typical experience of pain resolution after surgery, but that meaningful subpopulations of experience may exist. They also indicate that a transition occurs within 1 month after surgery from 1 pattern of change in pain over time to another.

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Unravelling the Relationship between Parent and Child PTSD and Pediatric Chronic Pain: the Mediating Role of Pain Catastrophizing

• Child pain catastrophizing mediates the relationship between child PTSD symptoms and child pain.• Child pain catastrophizing mediates the relationship between parent PTSD symptoms and child pain.• Child chronic pain treatment should address parent/child mental health symptoms.• Parent and child PTSD symptoms influence children's pain outcomes.

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IL-18 Contributes to Bone Cancer Pain by Regulating Glia Cells and Neuron Interaction

1. IL-18 signaling plays a critical role in bone cancer-induced pain.2. IL-18 signaling could induce GluN2B activation through Src kinase during bone cancer pain.3. IL-18-mediated microglia/astrocyte and microglia/neuron interactions in the dorsal horn.

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Sex-Specific Effects of Gender Identification on Pain Study Recruitment

• We measured gender in males and females, then asked them to participate in a pain study• Males who agreed to participate were higher in masculine gender identification• Aggressive and competitive males were most likely to participate

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AAPT Diagnostic Criteria for Chronic Abdominal, Pelvic, and Urogenital Pain: Irritable Bowel Syndrome

In conjuction with the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the US Food and Drug Administration and the American Pain Society (APS), the ACTTION-APS Pain Taxonomy (AAPT) initiative strove to develop the characteristics of a diagnostic system useful for clinical and research purposes across disciplines and types of chronic pain conditions. Following the establishment of these characteristics, a working group of clinicians and clinical and basic scientists with expertise in abdominal, pelvic, and urogenital pain began generating core diagnostic criteria and defining the related extraintestinal somatic pain and other symptoms experienced by patients.

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Painful groin in a young adult

A 24 year old man presented with a three year history of right groin pain, which was initially managed with physiotherapy for muscle strain. Pelvic radiography showed ill defined lytic lesions in the...

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Validity of clinical measures of smooth pursuit eye movement control in patients with idiopathic neck pain

Electrooculography is useful in detecting smooth pursuit neck torsion (SPNT) abnormalities in patients with neck pain, however, a validated, clinically relevant measure is lacking.

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Association of Prescription Drug Monitoring Program Use with Opioid Prescribing and Health Outcomes: a Comparison of Program Users and Non-Users

• We asked if a prescription drug monitoring program (PDMP) changed opioid risks.• We matched early PDMP registrants with similarly prescribing non-registrants.• Prescribing risk generally decreased among both registrants and non-registrants.• Frequent PDMP users showed similar trends to infrequent users.• Factors other than PDMP appeared to have greater influence on prescribing trends.

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A Cost-Analysis of an Interdisciplinary Pediatric Chronic Pain Clinic

• Pediatric chronic pain is a costly condition requiring interdisciplinary treatment• An interdisciplinary pain clinic reduced inpatient and emergency department visits• Pain clinic participation resulted in hospital cost savings of $36,228/patient/yr• Pain clinic participation resulted in insurance cost savings of $11,482/patient/yr

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Health leaders blame addiction for US opioid crisis

Alternative pain treatment options, reducing overprescribing, and destigmatizing misuse were among the potential solutions to the US opioid epidemic cited by healthcare leaders in a panel discussion...

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Effect of Upper limb Rehabilitation compared to No Upper limb Rehabilitation in Lung Transplant Recipients – A Randomized Controlled trial

Electroacupuncture alleviates chemotherapy-induced pain through inhibiting phosphorylation of spinal CaMKII in rats

Abstract

Background

Current medical treatments for chemotherapy-induced pain (CIP) are either ineffective or have adverse side effects. Acupuncture may alleviate CIP, but its effectiveness against this condition has not been studied. Paclitaxel causes neuropathic pain in cancer patients.

Methods

We evaluated the effects of electroacupuncture (EA) on paclitaxel-induced CIP in a rat model. Paclitaxel (2 mg/kg) or vehicle was injected (i.p.) on alternate days of 0–6. The resulting pain was treated with 10 Hz/2 mA/0.4 ms pulse EA for 30 min at the equivalent of human acupoint GB30 (Huantiao) once every other day between days 14 and 26. For sham control, EA needles were inserted into GB30 without stimulation. Von Frey filaments with bending forces of 2–8 g and 15 g were used to assess mechanical allodynia and hyperalgesia, respectively, on day 13 and once every other day between 14–26 days and then for 2–3 weeks after EA treatment.

Results

Compared to sham control, EA significantly alleviated paclitaxel-induced mechanical allodynia and hyperalgesia, as shown by less frequent withdrawal responses to the filaments. The alleviation of allodynia/hyperalgesia lasted up to 3 weeks after the EA treatment. EA significantly inhibited phosphorylation of Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) in the spinal cord. KN-93, a selective inhibitor of p-CaMKII, inhibited mechanical allodynia/hyperalgesia and p-CaMKII. 5-HT1A receptor antagonist blocked EA inhibition of allodynia/hyperalgesia and p-CaMKII.

Conclusions

Electroacupuncture activates 5-HT 1A receptors in the spinal cord and inhibits p-CaMKII to alleviate both allodynia and hyperalgesia. The data support acupuncture/EA as a complementary therapy for CIP.

Significance

Electroacupuncture (EA) activates spinal 5-HT1A receptors to inhibit p-CaMKII to alleviate paclitaxel-induced pain. Acupuncture/EA may be used as a complementary therapy for CIP.

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Bradykinin system is involved in endometriosis-related pain through endothelin-1 production

Abstract

Background

Endometriosis is a gynaecological disease exhibiting severe pelvic pain, but the mechanism of pain production remains unknown. Bradykinin (BK) is known as an inflammatory mediator, and shows elevated levels in inflammatory diseases such as rheumatoid arthritis. In the present study, we evaluated whether BK is involved in endometriosis-related pain.

Methods

Endometriotic lesions were used for immunohistochemistry. Primary cultures of endometriotic stromal cells (ESC) were stimulated with IL-1β and/or BK. Quantitative RT-PCR was used to evaluate the mRNA expressions of BK receptors (BKR) and endothelin-1 in ESC. The concentration of endothelin-1 in cystic fluid of endometrioma or non-endometrioma was measured with ELISA. The conditioned medium of ESC stimulated with IL-1β and/or BK was injected intraplantarly in mice, and evaluated whether pain-related licking behaviour was elicited.

Results

The expressions of BK and BKR in endometriotic lesions were observed by immunohistochemistry. In vitro experiments showed that IL-1β induced BKR-B1 and B2 on ESC. Activation of these receptors by BK significantly induced endothelin-1 expression in ESC, which was negated completely by HOE-140, a BKR-B2 antagonist. The cystic fluid of endometrioma contained higher amount of endothelin-1 compared to non-endometrioma. Intraplantar injection of the conditioned medium of ESC treated with IL-1β and BK significantly induced licking behaviour, which was suppressed with BQ-123, an endothelin type-A receptor antagonist.

Conclusions

The present study demonstrated the presence and the function of the BK axis in endometriosis, and established a potential new therapy target for endometriosis-related pain.

Significance

The present study demonstrated (1) the presence and the function of the BK system in endometriosis, (2) activation of BKR induced endothelin-1 in endometriotic lesion and (3) blocking endothelin-1 was effective to decrease pain.

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Association of insomnia severity with well-being, quality of life and health care costs: A cross-sectional study in older adults with chronic pain (PainS65+)

Abstract

Background

Insomnia is one of the most common complaints in chronic pain. This study aimed to evaluate the association of insomnia with well-being, quality of life and health care costs.

Methods

The sample included 2790 older individuals (median age = 76; interquartile range [IQR] = 70–82) with chronic pain. The participants completed a postal survey assessing basic demographic data, pain intensity and frequency, height, weight, comorbidities, general well-being, quality of life and the insomnia severity index (ISI). Data on health care costs were calculated as costs per year (€ prices) and measured in terms of outpatient and inpatient care, pain drugs, total drugs and total health care costs.

Results

The overall fraction of clinical insomnia was 24.6% (moderate clinical insomnia: 21.9% [95% CI: 18.8–23.3]; severe clinical insomnia: 2.7% [95% CI: 1.6–3.2]). Persons who reported clinical insomnia were more likely to experience pain more frequently with higher pain intensity compared to those reported no clinically significant insomnia. Mean total health care costs were € 8469 (95% CI: €4029-€14,271) for persons with severe insomnia compared with € 4345 (95% CI: €4033-€4694) for persons with no clinically significant insomnia. An association between severe insomnia, well-being, quality of life, outpatient care, total drugs costs and total health care costs remained after controlling for age, sex, pain intensity, frequency, body mass index and comorbidities using linear regression models.

Conclusions

Our results determine an independent association of insomnia with low health-related quality of life and increased health care costs in older adults with chronic pain.

Significance

The concurrence and the severity of insomnia among older adults with chronic pain were associated with decreased well-being and quality of life, and increased health care costs to society.

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Efficacy, tolerability and safety of cannabis-based medicines for chronic pain management – An overview of systematic reviews

Abstract

Medicinal cannabis has already entered mainstream medicine in some countries. This systematic review (SR) aimed at evaluating the efficacy, acceptability and safety of cannabis-based medicines for chronic pain management. Qualitative systematic review of SRs of randomized controlled trials with cannabis-based medicines for chronic pain management. The Cochrane databases of SRs, Database of Abstracts of Reviews of Effects and PubMed were searched for SR published in the period January 2009 to January 2017. Assessment of the methodological quality of SR was performed by the AMSTAR checklist. Out of 748 papers identified, 10 SRs met the inclusion criteria. The methodological quality was high in four and moderate in six SRs. There were inconsistent findings of four SRs on the efficacy of cannabis-based medicines in neuropathic pain and of one SR for painful spasms in multiple sclerosis. There were consistent results that there was insufficient evidence of any cannabis-based medicine for pain management in patients with rheumatic diseases (three SRs) and in cancer pain (two SRs). Cannabis-based medicines undoubtedly enrich the possibilities of drug treatment of chronic pain conditions. It remains the responsibility of the health care community to continue to pursue rigorous study of cannabis-based medicines to provide evidence that meets the standard of 21st century clinical care.

Significance

We provide an overview of systematic reviews on the efficacy, tolerability and safety of cannabis-based medicines for chronic pain management. There are inconsistent findings of the efficacy of cannabinoids in neuropathic pain and painful spasms in multiple sclerosis. There are inconsistent results on tolerability and safety of cannabis-based medicines for any chronic pain.

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Thoracic manual therapy is not more effective than placebo thoracic manual therapy in patients with shoulder dysfunctions: A systematic review with meta-analysis

Manual treatments targeting different regions (shoulder, cervical spine, thoracic spine, ribs) have been studied to deal with patients complaining of shoulder pain. Thoracic manual treatments seem able to produce beneficial effects on this group of patients. However, it is not clear whether the patient improvement is a consequence of thoracic manual therapy or a placebo effect.

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Structural and Functional Brain Changes at Early and Late Stages of Complex Regional Pain Syndrome

• We studied structural and functional brain changes at early and late stages of CRPS• GM volume, perfusion and SMN connectivity showed differences between the two stages• SMN changes at both stages showed impairment of higher orders of motor controls

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Comparing Pain and Depressive Symptoms of Chronic Opioid Therapy Patients Receiving Dose Reduction and Risk Mitigation Initiatives to Usual Care

• Limits placed on high-dose opioid prescribing did not impact pain or depression• Most patients had severe pain and reported opioids were very or extremely helpful• Most patients found opioid side effects were not at all or a little bothersome

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Which pain medications are effective for sciatica (radicular leg pain)?

What you need to knowThe most effective pain medication to treat patients with sciatica or radicular leg pain is unclearIn approximately one third of patients, symptoms improve within two weeks; in...

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Prior Mental Disorders and Subsequent Onset of Chronic Back or Neck Pain: Findings From 19 Countries.

• Chronic back/neck pain is common in the general adult population, affecting 20-30%• Most mental disorders are associated with subsequent chronic back/neck pain• The greater the number of mental disorders, the greater the associated risk of pain• Early detection and treatment of mental disorders may help prevent later pain onset• Back/neck pain assessment in psychiatric services may help reduce disability

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γ-Aminobutyric acid (GABA) oral rinse reduces capsaicin-induced burning mouth pain sensation: An experimental quantitative sensory testing study in healthy subjects

Abstract

Background

In burning mouth patients, analgesia after oral administration of clonazepam may result from modulation of peripheral γ-aminobutyric acid (GABA) receptors.

Methods

The effect of oral administration of test solutions (water, 0.5 mol/L or 0.05 mol/L GABA, 1% lidocaine) was investigated for the amelioration of pain and sensitivity induced by application of capsaicin (1%, 2 min) to the tongue of thirty healthy male and female subjects in this four-session, randomized, placebo-controlled, double-blinded, cross-over study. Intra-oral quantitative sensory testing was used to assess cold (CDT), warm (WDT) and mechanical (MDT) detection thresholds as well as mechanical (MPT) and heat (HPT) pain thresholds. Capsaicin-induced pain intensity was continuously rated on a 0–10 electronic visual analogue scale (VAS). The area under the VAS curve (VASAUC) after rinsing was calculated for each solution.

Results

Capsaicin application on the tongue evoked burning pain with a peak of 4.8/10, and significantly increased CDT and MDT while significantly decreasing WDT, HPT, and MPT. The VASAUC was significantly smaller after oral rinse with 0.05 mol/L GABA, 0.5 mol/L GABA, and 1% lidocaine than after oral rinse with water. Rinse with 0.5 mol/L or 0.05 mol/L GABA were similarly effective in decreasing VASAUC. Rinsing with either 1% lidocaine, 0.5 mol/L or 0.05 mol/L GABA also significantly attenuated the effects of capsaicin on WDT and HPT in a treatment independent manner. There were no sex-related differences in these effects of GABA.

Conclusions

Capsaicin-induced burning tongue pain and decreases in WDT and HPT can be ameliorated by rinsing the mouth with lidocaine and GABA solutions.

Significance

Rinsing the mouth with an oral GABA containing solution ameliorated burning pain and increased heat sensitivity produced by application of capsaicin to the tongue. This finding suggests that GABA can act as a local analgesic agent in the oral cavity.

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Pain Affects Visual Orientation: an Eye-Tracking Study

• Pain affects attentional shifts in terms of eye-movements.• Pain reduced exploratory behavior (less saccades and longer fixations).• It is unclear so far how this might apply to chronic pain conditions.

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Gender and the Association between Long-Term Prescription Opioid Use and New Onset Depression

• Increased risk of depression following >90 days opioid use for both genders.• Female vs. male veterans have greater depression risk after >90 days opioid use.• No gender difference in opioid-depression risk was found in the private sector.• Need closer monitoring of mood associated with chronic opioid use for some groups.

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Postoperative rehabilitation following thumb base surgery: a systematic review of the literature

Issue Information

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The Concept of Contexts in Pain: Generalization of Contextual Pain-Related Fear Within a De Novo Category of Unique Contexts

• Unpredictable pain induces contextual pain-related fear.• Category-level generalization involves conceptual (instead of perceptual) similarity.• Contextual pain-related fear spreads to novel conceptually related contexts.• Fear generalization was manifest in the self-reports, but not in startle measures.

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The β-lactam clavulanic acid mediates glutamate transport-sensitive pain relief in a rat model of neuropathic pain

Abstract

Background

Following nerve injury, down-regulation of astroglial glutamate transporters (GluTs) with subsequent extracellular glutamate accumulation is a key factor contributing to hyperexcitability within the spinal dorsal horn. Some β-lactam antibiotics can up-regulate GluTs, one of which, ceftriaxone, displays analgesic effects in rodent chronic pain models.

Methods

Here, the antinociceptive actions of another β-lactam clavulanic acid, which possesses negligible antibiotic activity, were compared with ceftriaxone in rats with chronic constriction injury (CCI)-induced neuropathic pain. In addition, the protein expression of glutamate transporter-1 (GLT1), its splice variant GLT1b and glutamate-aspartate transporter (GLAST) was measured in the spinal cord of CCI rats. Finally, protein expression of the same GluTs was evaluated in cultured astrocytes obtained from rodents and humans.

Results

Repeated injection of ceftriaxone or clavulanic acid over 10 days alleviated CCI-induced mechanical hypersensitivity, whilst clavulanic acid was additionally able to affect the thermal hypersensitivity. In addition, clavulanic acid up-regulated expression of GLT1b within the spinal cord of CCI rats, whereas ceftriaxone failed to modulate expression of any GluTs in this model. However, both clavulanic acid and ceftriaxone up-regulated GLT1 expression in rat cortical and human spinal astrocyte cultures. Furthermore, clavulanic acid increased expression of GLT1b and GLAST in rat astrocytes in a dose-dependent manner.

Conclusions

Thus, clavulanic acid up-regulates GluTs in cultured rodent- and human astroglia and alleviates CCI-induced hypersensitivity, most likely through up-regulation of GLT1b in spinal dorsal horn.

Significance

Chronic dosing of clavulanic acid alleviates neuropathic pain in rats and up-regulates glutamate transporters both in vitro and in vivo. Crucially, a similar up-regulation of glutamate transporters in human spinal astrocytes by clavulanic acid supports the development of novel β-lactam-based analgesics, devoid of antibacterial activity, for the clinical treatment of chronic pain.

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Characterization of a novel capsaicin/heat ongoing pain model

Abstract

Background

Human experimental pain models provide an important translational link between pre-clinical models and clinical pain. Using topical capsaicin and continuous heat application, the novel capsaicin/heat ongoing pain (CHOP) model induces long-lasting experimental pain of which the perceived intensity can be individually adjusted.

Methods

In the CHOP model, capsaicin or control cream is applied to a 10 × 10 cm skin area and a heating pad is applied over the area after cream removal. Two experiments in healthy participants were performed for model characterization. In Experiment 1, a constant temperature was applied for 60 min; in Experiment 2, temperature was adjusted to maintain a constant perceived intensity for 60 min.

Results

Experiment 1: across participants, constant temperature induced initial habituation followed by an increase in sensation back to baseline. Cluster analysis revealed that half the participants sensitized to the constant temperature, while the other half did not. The degree of sensitization was related to the baseline pain unpleasantness, relative to pain intensity. Experiment 2: constant perceived intensity was achieved in the painful and a non-painful control condition. The two conditions did not differ regarding possibly confounding variables, including blood pressure, heart rate, inflammation or physiological stress as measured by surrogate markers. Secondary allodynia and hyperalgesia were reported more following painful compared to control stimulation. Sensitizers as determined in Experiment 1 were also more pain sensitive in Experiment 2.

Conclusion

The CHOP model reproduces some aspects of clinical pain, such as longer duration, sensitization, secondary allodynia and hyperalgesia.

Significance

Here we demonstrate a novel pain model that can be applied for up to an hour without tissue damage. The CHOP model allows for investigation of primary and secondary hyperalgesia as well as top-down influences on sensitization, thereby providing an experimental model that can be used to assess clinically-oriented questions.

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Efficacy, acceptability and safety of cognitive behavioural therapies in fibromyalgia syndrome – A systematic review and meta-analysis of randomized controlled trials

Abstract

This updated systematic review aimed at evaluating the efficacy, acceptability and safety of cognitive behavioural therapies (CBTs) in fibromyalgia syndrome (FMS). Clinicaltrials.gov, Cochrane Library, MEDLINE, PsycINFO and SCOPUS were searched from September 2013 to May 2017. Randomized controlled trials (RCTs) comparing CBTs with controls were analysed. Primary outcomes were ≥50% pain relief, ≥20% improvement of health-related quality of life (HRQoL), negative mood, fatigue, disability, acceptability and safety at end of therapy and at 6 months follow-up. Effects were summarized by a random effects model using risk differences (RD) or standardized mean differences (SMD) with 95% confidence intervals (CI). 29 RCTs with 2509 subjects were included. CBTs were superior to controls (waiting list, attention control, treatment as usual, other active non-pharmacological therapies) in pain relief of 50% or greater (RD 0.05 [95% CI 0.02–0.07] (high-quality evidence), improvement of HRQoL of 20% or greater (RD 0.13 [95% CI 0.00–0.26], (moderate quality evidence), and in reducing negative mood (SMD −0.43 [95% CI −0.62 to −0.24]) (high-quality evidence), disability (SMD −0.30 [95% CI −0.52 to −0.08]) (high-quality evidence) and fatigue (SMD – 0–27 [95% CI −0.50 to −0.03]) (high-quality evidence). There were no statistically significant differences between CBTs and controls in acceptability and safety (high-quality evidence). The update did not change the major findings of the previous review. CBTs provided a clinically relevant benefit over control interventions in reducing some key symptoms of FMS and disability at the end of treatment.

Significance

This updated systematic review with meta-analysis on cognitive behavioural therapies (CBTs) including acceptance-based CBTs endorse the efficacy and tolerability of CBTs in reducing key symptoms and disability in FMS in the short- and long-term if compared to waiting list, treatment as usual, attention controls and active non-pharmacological therapies. CBTs did not differ in efficacy except superiority for coping with pain and tolerability from recommended drug therapy (pregabalin and/or duloxetine).

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Salvinorin A reduces neuropathic nociception in the insular cortex of the rat

Abstract

Background

Neuropathic pain is one of the most important challenges in public health. The search for novel treatments is important for an adequate relief without adverse effects. In this sense salvinorin A (SA), the main diterpene of the medicinal plant Salvia divinorum is an important antinociceptive compound, which acts as a potent agonist of kappa opioid receptor (KOR) and cannabinoid CB1 receptors.

Methods

We evaluated nociceptive responses in a neuropathic pain model induced by the sciatic nerve ligature (SNL) in the right hind paw, after the microinjection of SA, Salvinorin B (SB), KOR and CB1 antagonists directly in the insular cortex (IC) in male wistar rats.

Results

We found a potent antinociceptive effect with the administration of SA. Moreover, this effect was blocked by the administration of a KOR antagonist as well as the administration of a CB1 antagonist.

Conclusion

Salvinorin A has a potent antinociceptive effect when is administered centrally in the IC by the interaction with KOR and CB1 receptors.

Significance

We show evidence on the effectiveness of the administration of salvinorin A in the IC in a rodent model of neuropathic pain. These results support the use of novel compounds like SA as a therapeutic alternative for neuropathic pain relief.

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Ten-year prevalence of mental disorders in patients presenting with chronic pain in secondary care: A register linkage cohort study

Abstract

Background

Prevalence rates of mental disorders in patients with chronic pain vary and may be overestimated when assessed by screening instruments only. Objectives were to estimate the 10-year prevalence of different mental disorders diagnosed by psychiatrists in patients with chronic pain compared with the Danish general population.

Methods

Patients (n = 7197) consulted in the interdisciplinary Pain Clinic South at Odense University Hospital, Denmark, from 2005 to 2015 were included. Data from the Pain Clinic were linked to the Danish National Patient Register-Psychiatry and the Danish Civil Registration System. Age and gender standardized prevalence ratios (SPR) were calculated.

Results

In all, 17.8% of patients with chronic pain had been diagnosed with a mental disorder. The most frequent diagnoses were adjustment disorders (subcategory of anxiety disorders) (8.9%), depression (6.1%), personality disorders (3.8%), and substance abuse disorders (3.5%). Women and men with chronic pain had higher rates of anxiety disorders (SPR 3.1; 95% CI 2.9–3.4) and depression (SPR 2.5; 95% CI 2.3–2.8), whereas men had higher rates of substance abuse disorders (SPR 1.6; 95% CI 1.3–1.9) than found for the general population.

Conclusions

Although depression and anxiety were noted more frequently among patients with chronic pain than the general population, prevalence rates were lower than previously reported. The most frequent diagnoses were adjustment disorders.

Significance

Prevalence rates of anxiety and depression diagnosed by psychiatrists in patients with chronic pain were found to be lower than previous findings using screening instruments. Adjustment disorders were the most frequent disorders diagnosed, as this study is the first to investigate.

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Usage of Chewing Gum in Posterior Spinal Fusion Surgery for Adolescent Idiopathic Scoliosis: A Randomized Controlled Trial

Study Design. Randomized controlled trial. Objective. The present study investigated the effectiveness of chewing gum on promoting faster bowel function and its ability to hasten recovery for patients with adolescent idiopathic scoliosis (AIS) after posterior spinal fusion (PSF) surgery. Summary of Background Data. Sham feeding with chewing gum had been reported to reduce the incidence of postoperative ileus by accelerating recovery of bowel function. Methods. We prospectively recruited and randomized 60 patients with AIS scheduled for PSF surgery into treatment (chewing gum) and control group. The patient-controlled anesthesia usage, wound pain score, abdominal pain score, nausea score, and abdominal girth were assessed and recorded at 12, 24, 36, 48, and 60 hours postoperatively. The timing for the first fluid intake, first oral intake, sitting up, walking, first flatus after surgery, first bowel opening after surgery, and duration of hospital stay were also assessed and recorded. Results. We found that there were no significant differences (P > 0.05) in patient-controlled anesthesia usage, wound pain score, abdominal pain score, nausea score, and abdominal girth between treatment (chewing gum) and control groups. We also found that there were no significant difference (P > 0.05) in postoperative recovery parameters, which were the first fluid intake, first oral intake, sitting up after surgery, walking after surgery, first flatus after surgery, first bowel opening after surgery, and duration of hospital stay between both groups. The wound pain was the worst at 12 hours postoperatively, which progressively improved in both groups. The abdominal pain progressively worsened to the highest score at 48 hours in the treatment group and 36 hours in the control group before improving after that. The pattern of severity and recovery of wound pain and abdominal pain was different. Conclusion. We found that chewing gum did not significantly reduce the abdominal pain, promote faster bowel function, or hasten patient recovery. Level of Evidence: 1

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Nerve Root Compression Increases Spinal Astrocytic Vimentin in Parallel With Sustained Pain and Endothelial Vimentin in Association With Spinal Vascular Reestablishment

Study Design. Temporal immunohistochemistry analysis of spinal cord tissue from a rat model of cervical radiculopathy. Objective. The goal was to measure spinal endothelial and astrocytic vimentin expression after a painful nerve root compression to define spinal cellular expression of vimentin in the context of pain. Summary of Background Data. The intermediate filament, vimentin, is expressed in a variety of cell types in the spinal cord and is modulated in response to neural pathologies. Early after nerve root compression spinal astrocytes become activated and blood-spinal cord barrier (BSCB) breakdown occurs in parallel with development of pain-related behaviors; these spinal responses remain activated as does the presence of pain. In addition to vimentin, glial fibrillary acidic protein (GFAP) expression is a hallmark of astrocyte activation. In contrast, vascular endothelial cells down-regulate vimentin expression in parallel with vascular breakdown. It is not known whether spinal astrocytes and endothelial cells modulate their expression of vimentin in response to a painful neural injury. Methods. Mechanical hyperalgesia was measured and spinal cord tissue was harvested at days 1 and 7 after a unilateral nerve root compression in rats. Vimentin was coimmunolabeled with GFAP to label astrocytes and von Willebrand factor (VWF) for endothelial cells in the spinal cord on the side of injury. Results. Spinal astrocytic vimentin increases by day 7 after nerve root compression, corresponding to when mechanical hyperalgesia is maintained. Spinal endothelial vimentin increases as early as day 1 after a painful compression and is even more robust at day 7. Conclusion. The delayed elevation in spinal astrocytic vimentin corresponding to sustained mechanical hyperalgesia supports its having a relationship with pain maintenance. Further, since BSCB integrity has been shown to be reestablished by day 7 after a painful compression, endothelial expressed vimentin may help to fortify spinal vasculature contributing to BSCB stability. Level of Evidence: N/A

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One-stage Surgical Management for Lumbar Brucella Spondylitis by Posterior Debridement, Autogenous Bone Graft and Instrumentation: A Case Series of 24 Patients

Study Design. Clinical case series. Objective. The aim of this study was to explore the efficacy and safety of one-stage debridement, autogenous bone graft, and instrumentation for lumbar brucella spondylitis (LBS) via a posterior approach. Summary of Background Data. Reports on LBS are sporadic, and the therapeutic effect and safety of surgical interventions have not been assessed in clinical studies. Methods. Between January 2012 and January 2014, 24 consecutive patients with symptomatic LBS who underwent a one-stage operation that combined debridement, autogenous bone graft, and instrumentation via a posterior approach were enrolled. Back pain was measured using the visual analog scale (VAS). The neurological status was evaluated with the American Spinal Injury Association (ASIA) scale. Bone healing was evaluated based on postoperative plain x-ray or computed tomography. Results. All cases were followed up for an average of 14.3 + 3.5 months. The VAS scores were significantly improved at every follow-up interval. An improvement of at least one grade level was observed in the ASIA score of each patient. The average time of bone fusion was 6.8 + 1.6 months. Significant improvements of the average segmental Cobb angle was observed from a preoperative value of 18.4° + 4.6° to a last follow-up value of 21.1° ± 3.7°. At the last follow up, the titers of antibodies against the standard tube agglutination test, erythrocyte sedimentation rate, and C-reactive protein were negative for all patients. Conclusion. For LBS, systemic antibrucellosis chemotherapy is the cornerstone of treatment. When cauda equine syndrome, radiculopathy, spinal instability, and severe back pain caused by extradural nonabsorbable abscess or progressive collapse are present, surgical intervention is inevitable. One-stage debridement, autogenous bone graft, and instrumentation via a posterior approach could represent an alternative treatment for LBS, and the efficacy and safety of these techniques are satisfactory. Level of Evidence: 4

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Lumbar Spine Alignment in Six Common Postures: An ROM Analysis With Implications for Deformity Correction

Study Design. A cross-sectional study of prospectively collected data. Objective. To compare lumbar spine alignment in six common postures, and estimate loss in range of motion (ROM) relative to standing. Summary of Background Data. Ideal position for fusion of lumbar spine remains unknown. Although surgical fusion is necessary for deformity correction and symptom relief, the final position in which the vertebrae are immobilized should provide maximum residual function. Methods. Data were collected prospectively from 70 patients with low back pain recruited over a year. All subjects had x-rays performed in slump sitting, forward bending, supine, half squatting, standing, and backward bending postures. ROM quantified in terms of sagittal global and segmental Cobb angles was measured from L1 to S1. Loss of ROM relative to standing was calculated for each posture. Analysis of variance and unpaired t tests were used to identify differences in alignment between postures. Results. Slump sitting gives the greatest lumbar flexion followed by forward bending, and supine postures (P < 0.001). Backward bending produces greater lumbar extension than standing (P = 0.035). Half-squatting and standing postures were not significantly different (P = 0.938). For all postures, L4–5 and L5-S1 segments remained in lordosis, with L4–5 having greater ROM than L5-S1. L1–2 turns kyphotic in lying supine, L2–3 at forward bending, and L3–4 at slump sitting in the form of a “kyphosing cascade.” Should the entire lumbar spine be fused in standing position from L1-S1, there would likely be a mean loss of 47.6° of lumbar flexion and 5.9° of lumbar extension. Conclusion. The present study demonstrates the extent of flexibility required of the lumbar spine in assuming various postures. It also enables comparison of the differences in degree of motion occurring in the lumbar spine, both across postures and across segments. Significant loss in ROM, particularly flexion, is anticipated with fusion modeled after the lordotic standing lumbar spine. Level of Evidence: 2

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The Association Between Self-reported Low Back Pain and Radiographic Lumbar Disc Degeneration of the Cohort Hip and Cohort Knee (CHECK) Study

Study Design. Cross-sectional study, nested in a prospective cohort (Cohort Hip and Knee, CHECK). Objective. Low back pain (LBP) is very common and the main cause of activity limitations and work absence throughout the world. Although lumbar disc degeneration (LDD) is suggested as a cause of LBP, this association remains debatable. Therefore, this study assessed the association between the radiographic features of LDD and the presence of self-reported LBP, LBP persisting longer than 3 months, the perceived severity of LBP and presence of neuropathic pain. Summary of Background Data. Previous literature suggests an association between LBP and both the LDD definitions osteophytes and disc space narrowing. There are no studies that have explored the association between LDD and neuropathic pain. Methods. Associations between the radiographic LDD using two definitions (i.e., osteophytes, disc space narrowing) versus the presence of LBP, LBP > 3 months, severe LBP and neuropathic pain, were analyzed with logistic regression models. Results. A total of 699 participants completed the questionnaire and had a lumbar radiograph. Radiographs were scored by two independent observers. Osteophytes were present in 98% of the population and disc space narrowing in 67%. Osteophytes were not significantly associated with LBP (OR = 1.2, 95% CI 0.9–1.7). Disc space narrowing was significantly associated with the presence of LBP and neuropathic pain (OR = 1.7, 95% CI = 1.2–2.4 and OR 1.7, 95% CI 1.1–2.7, respectively). The presence of a LBP severity score of ≥4, and LBP persisting > 3 months were not significantly associated with the two definitions of LDD. Conclusion. This study shows the presence of an association between disc space narrowing, whereas no association was found between osteophytes and LBP. We are the first to report an association between disc space narrowing and neuropathic pain. Level of Evidence: 3

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Measurement Properties of the NIH-Minimal Dataset Dutch Language Version in Patients With Chronic Low Back Pain

Study Design. Validation study with cross-sectional and longitudinal measurements. Objective. To translate the US National Institutes of Health (NIH)-minimal dataset for clinical research on chronic low back pain into the Dutch language and to test its validity and reliability among people with chronic low back pain. Summary of Background Data. The NIH developed a minimal dataset to encourage more complete and consistent reporting of clinical research and to be able to compare studies across countries in patients with low back pain. In the Netherlands, the NIH-minimal dataset has not been translated before and measurement properties are unknown. Methods. Cross-cultural validity was tested by a formal forward-backward translation. Structural validity was tested with exploratory factor analyses (comparative fit index, Tucker-Lewis index, and root mean square error of approximation). Hypothesis testing was performed to compare subscales of the NIH dataset with the Pain Disability Index and the EurQol-5D (Pearson correlation coefficients). Internal consistency was tested with Cronbach α and test-retest reliability at 2 weeks was calculated in a subsample of patients with Intraclass Correlation Coefficients and weighted Kappa (κω). Results. In total, 452 patients were included of which 52 were included for the test-retest study. Validity: factor analysis for structural validity pointed into the direction of a seven-factor model (Cronbach α = 0.78). Factors and total score of the NIH-minimal dataset showed fair to good correlations with Pain Disability Index (r = 0.43–0.70) and EuroQol-5D (r = −0.41 to −0.64). Reliability: test-retest reliability per item showed substantial agreement (κω=0.65). Test-retest reliability per factor was moderate to good (Intraclass Correlation Coefficient = 0.71). Conclusion. The Dutch language version measurement properties of the NIH-minimal were satisfactory. Level of Evidence: N/A

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Quebec Serve and Protect Low Back Pain Study: A Web-based Cross-sectional Investigation of Prevalence and Functional Impact Among Police Officers

Study Design. Web-based cross-sectional study. Objective. The aim of this study was to describe the prevalence and the burden of low back pain (LBP) and chronic low back pain (CLBP) among Quebec police officers. Summary of Background Data. Police officers have work-related factors associated with LBP, but chronicity and impacts of this condition have been little explored among this population. Methods. Between May and October 2014, a web-based cross-sectional study was conducted among police officers working in the province of Quebec (Canada). Nine police organizations accepted to disseminate the email invitation to their members. The survey included the French-Canadian version of the Nordic Musculoskeletal Questionnaire and other items regarding functional impact of LBP and associated treatments. Results. A total of 3589 police officers completed the questionnaire. Mean age was 38.5 ± 8.7 years, 32.0% were women, and 67.4% reported being car-patrol officers. A majority reported LBP symptoms in the past 12 months (67.7%) and 96.5% of them perceived that presence of LBP was totally/partially linked to their work in the police force. Prevalence of CLBP among all responders was 28.7%. Police officers reporting CLBP, as compared to those reporting acute or subacute LBP symptoms in the past 12 months, were more likely to report LBP-related reduction of work activities (64.4% vs. 45.7%; P < 0.001) and more working days lost in the past 12 months (average of 11.9 ± 43.5 vs. 1.5 ± 9.8; P < 0.001). A greater proportion also reported LBP-related health care visits in the past 12 months (86.2% vs. 64.2%; P < 0.001) and current use of pain medications/complementary alternative medicines (90.1% vs. 69.7%; P < 0.001). Conclusion. CLBP is a frequent and burdensome condition among Quebec police officers. Our results underline the importance for police organizations to promote CLBP prevention and to implement workplace management programs. Level of Evidence: 3

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Investigating the Association Between Lower Extremity and Low Back Symptoms Among Saskatchewan Farmers Using the Standardized Nordic Questionnaire

Study Design. Cross-sectional survey. Objective. The aim of this study was to investigate the association between self-reported low back symptoms and symptoms in the hip, knee, and ankle in a high-risk occupational group. Summary of Background Data. Low back pain, with or without lower extremity referral, poses a major challenge to occupational productivity, especially in farming. Although low back symptoms can occur independent of lower extremity symptoms, anatomical positioning of nerves supplying the lower limbs means structural and physiological changes in the spine can lead to referred pain in the lower limbs, but the magnitude of the association between low back and lower extremity symptoms is unclear. Methods. Baseline postal questionnaire data from the Saskatchewan Farm Injury Cohort Study yielded surveys from 2653 adults from 1020 farms, who responded to Standardized Nordic Questionnaire (SNQ) items on “ache, pain, discomfort” in nine body parts during the last 12 months. Bivariate and multivariate regression modeling was performed with low back symptoms as the outcome and lower extremity symptoms as the independent variable. Results. After adjustment for age, sex, depression, and heavy lifting, low back symptom was significantly related with hip pain (odds ratio [OR] = 3.84, 95% confidence interval [CI] 3.04–4.84), knee pain (OR = 1.84, 95% CI 1.49–2.28), and ankle pain (OR = 1.79, 95% CI 1.40–2.29). Results showed a significant but decreasing relationship to low back symptoms as sites became more distal. Conclusion. Hip and low back symptoms are highly associated, suggesting a common mechanism may be at work. Although there appears be increased risk of knee and ankle region symptoms among those with back pain, the SNQ is not designed to differentiate types of referred symptoms (i.e., numbness, tingling, shooting pain) and/or clinical diagnoses. Other tools, possibly corroborated with clinical examination findings, are likely necessary for a more thorough investigation of referred pain patterns in this high-risk occupational group. Level of Evidence: 3

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Risk Factors for Poor Patient-Reported Quality of Life Outcomes After Posterior Lumbar Interbody Fusion: An Analysis of 2-Year Follow-up

Study Design. A retrospective review of prospectively collected data. Objective. The present study aimed to identify risk factors for poor patient-reported quality of life (QOL) outcomes, based on five categories (pain-related disorders, lumbar spine dysfunction, gait disturbance, social life dysfunction, and psychological disorders) of the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), after posterior lumbar interbody fusion (PLIF) at the 2-year follow-up. Summary of Background Data. Many studies have been reported on patient QOL outcomes after lumbar surgery; however, few reports have focused on risk factors for poor postoperative QOL outcomes in terms of the various disabilities and dysfunctions after PLIF. Methods. One hundred consecutive patients (39 men and 61 women; mean age 69.6 [44–84] yr) who underwent single- or two-level PLIF for degenerative spondylolisthesis and/or foraminal stenosis with a 2-year follow-up were included. The effectiveness of surgery in each category of the JOABPEQ was evaluated. Demographic and clinical data and radiographic parameters were reviewed. Risk factors for poor postoperative QOL outcomes in each category of the JOABPEQ were investigated by multivariate logistic regression analysis. Results. Older age and spinopelvic malalignment (preoperative high pelvic tilt or postoperative decrease in lumbar lordosis [=postoperative increase in the mismatch between pelvic incidence and lumbar lordosis]) were risk factors for poor postoperative QOL outcomes in all categories of the JOABPEQ, except for lumbar spine dysfunction. In contrast, increase in number of PLIF segments, non-union, and radiographic adjacent segment degeneration were risk factors for poor postoperative QOL outcomes in lumbar spine dysfunction and gait disturbance. Conclusion. The risk factors for poor QOL outcomes after PLIF differed among the five categories of the JOABPEQ. In particular, surgery-related factors (e.g., increase in number of PLIF segments, nonunion, and radiographic adjacent segment degeneration) had a negative effect on the improvement of lumbar spine dysfunction and gait disturbance. Level of Evidence: 4

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