[Correspondence] Informing women with endometriosis about ovarian cancer risk

We acknowledge the ongoing concerns of women with endometriosis, a chronic gynaecological condition affecting about 176 million women worldwide, regarding information about their increased ovarian cancer risk. Endometriosis is an inflammatory disease process characterised by lesions of endometrial-like tissue outside the uterus—commonly on the pelvic peritoneum and ovaries—that is associated with debilitating pelvic pain and infertility.1 Although benign, endometriosis has cancer-like features,2 a mutation profile similar to that of ovarian cancer,3 and an increased ovarian cancer risk.

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Dimensionality and Reliability of the Central Sensitization Inventory (CSI) in a Pooled Multi-Country Sample

• A multi-country examination of CSI dimensionality determined the best fit was a bi-factor model• Bifactor model fitted CSI structure better than unidimensional and the four-factor models.• Only total CSI scores should be used and reported.

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Acupuncture for Chronic Pain: Update of an Individual Patient Data Meta-Analysis

- Acupuncture has a clinically relevant effect on chronic pain that persists over time- The effect of acupuncture cannot be explained only by placebo effects- Factors in addition to the specific effects of needling are important contributors- Referral for acupuncture treatment is a reasonable option for chronic pain patients

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Power through the ages

Power through the ages

Nature 551, 7682 (2017). doi:10.1038/d41586-017-07506-z

Author: Stephanie Pain

From elbow grease to electricity, horsepower to hydropower, energy has played a crucial part in shaping society.

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Endogenous Pain Modulation Induced by Extrinsic and Intrinsic Psychological Threat in Healthy Individuals

• Observing pain in another induces endogenous analgesia.• Threat of pain to oneself also initiates endogenous analgesia.• Endogenous analgesia was observed in the absence of any somatosensory afferent input.• Intrinsic/extrinsic threat cues may be important in noxious CPM paradigms.

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Ketamine for chronic non-cancer pain: A meta-analysis and trial sequential analysis of randomized controlled trials

Abstract

Background

Ketamine has been suggested to be efficient in relieving chronic pain. However, there is inconsistency across studies investigating the effect of ketamine for chronic pain management. We aimed to perform a meta-analysis in order to assess the efficacy of this compound during chronic non-cancer pain conditions.

Methods

The study consisted in a meta-analysis of clinical trials comparing ketamine to a placebo during chronic non-cancer pain. The primary endpoint of this study was pain relief 4 weeks after the beginning of treatment. Secondary outcomes were: pain relief 1, 2, 8 and 12 weeks after the beginning of treatment and incidence of psychedelic manifestations.

Results

Six studies were included in this meta-analysis. Overall, 99 patients received ketamine and 96 received placebo. Ketamine did not decrease pain intensity at 4 weeks (MD (on a 0 to 10 scale) = −1.12 [−2.33, 0.09], GRADE evidence: very low). However, analysing studies with no high-risk bias found ketamine to decrease pain intensity at 4 weeks and increased the level of GRADE evidence to moderate. Trial sequential analysis confirmed the overall result and revealed the lack of power of this meta-analysis. Ketamine also decreased pain intensity at all other evaluated points in time. Ketamine increased the incidence of psychedelic manifestations in comparison to placebo.

Conclusion

Results of this meta-analysis found moderate evidence suggesting the efficacy of ketamine during chronic pain. Further studies are warranted to conclude about the effect of ketamine during chronic pain conditions and to determine optimal administration regimes of this agent during this condition.

Significance

Ketamine has been found interesting for managing chronic pain. We performed a meta-analysis aiming to confirm those results. Ketamine was found efficient in alleviating pain up to 12 weeks after the beginning of treatment. However, overall evidence favouring the use of this compound was very low.

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[Perspectives] Powerful venom

It can't be said that Venom: Killer and Cure, the new exhibition at the Natural History Museum in London, UK, will set your mind at ease. Never mind the giant cobra straight out of B-movie nightmare or the huge, hairy (but harmless to humans) Burgundy Goliath birdeater tarantula; it's the insects that are the worst. A chilling display of nasty little bugs accompanies each one with a description of the effects of their sting. That of the trap-jaw ant is “instantaneous and excruciating: a rat trap snaps your fingernail”; the bullet ant induces “pure, intense, brilliant pain, like walking over flaming charcoal with a three-inch nail embedded in your feet”; and the warrior wasp will convince you that “you are chained in the flow of an active volcano”.

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Metastatic adenocarcinoma masquerading as panuveitis

A 47 year old woman presented with redness, pain, blurred vision, and a fluffy mass in her right eye (fig 1). On examination, there was conjunctival congestion, keratic precipitates, retinal...

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A teenage girl with lower abdominal pain

A 14 year old girl arrived with her mother at the emergency department complaining of a 6 day history of lower abdominal pain, associated with dysuria and mild fever. She reported no other symptoms....

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Identifying risk factors for first-episode neck pain: A systematic review

Neck pain affects 15.1% of the United States' general population every 3 months, and ranks fourth in global disability. Because of the tendency for neck pain to become a chronic issue, it is important to identify risk factors that could encourage prevention and early diagnosis. The purpose of this systematic review was to identify risk factors for a first episode of neck pain. Three databases were searched with key words such as “neck pain” and “first incidence.” Risk factors from the resulting articles were reported as either a physical or psychosocial risk factor and ranked by the strength of their odds/risk/hazard ratio: <1.0 (protective factor), 1.0–1.5 (minor risk), 1.5–2.0 (moderate risk), or 2.0+ (major risk).

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The Influence of Social Threat on Pain, Aggression, and Empathy in Women

• Social threat is associated with increased threat value of pain.• Social threat also increases aggression and reduces empathy towards others.• Social threat did not affect painful facial expression or pain intensity and unpleasantness ratings.

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Hijacking the endogenous opioid system to treat pain: who thought it would be so complicated?

No abstract available

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Discovery of endogenous opioid systems: what it has meant for the clinician's understanding of pain and its treatment

Abstract Before the discovery of the endogenous opioid system in the 1970s, opioids were understood only through the lens of opioid drug effects. Opium produced sleep, pain relief, and addiction. Once a variety of opioids had been extracted from opium, and still others synthesized chemically, it became clear that there must be endogenous receptors to explain differential drug effects. So, the search was on to identify the receptors, and subsequently their endogenous ligands. Even then, the consequential ways in which the endogenous opioid system influences the way we respond to the environment and survive took time to unravel. Today's understanding extends far beyond simply accepting pain relief and addiction as separate processes, to the realization that the endogenous opioid system achieves constant adjustments between punishment (pain) and reward in communicating areas of the brain previously thought to subserve separate functions. The system also plays a crucial role in socialization. Taken together, these 2 lines of research have led to new insights into why the endogenous opioid system is so important in terms of evolution, individual survival and day-to-day function, and how important it is to consider opioid medications within the context of these critical natural functions.

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Tumor necrosis factor alpha secreted from oral squamous cell carcinoma contributes to cancer pain and associated inflammation

Abstract Patients with oral cancer report severe pain during function. Inflammation plays a role in the oral cancer microenvironment; however, the role of immune cells and associated secretion of inflammatory mediators in oral cancer pain has not been well defined. In this study, we used 2 oral cancer mouse models: a cell line supernatant injection model and the 4-nitroquinoline-1-oxide (4NQO) chemical carcinogenesis model. We used the 2 models to study changes in immune cell infiltrate and orofacial nociception associated with oral squamous cell carcinoma (oSCC). Oral cancer cell line supernatant inoculation and 4NQO-induced oSCC resulted in functional allodynia and neuronal sensitization of trigeminal tongue afferent neurons. Although the infiltration of immune cells is a prominent component of both oral cancer models, our use of immune-deficient mice demonstrated that oral cancer–induced nociception was not dependent on the inflammatory component. Furthermore, the inflammatory cytokine, tumor necrosis factor alpha (TNFα), was identified in high concentration in oral cancer cell line supernatant and in the tongue tissue of 4NQO-treated mice with oSCC. Inhibition of TNFα signaling abolished oral cancer cell line supernatant-evoked functional allodynia and disrupted T-cell infiltration. With these data, we identified TNFα as a prominent mediator in oral cancer–induced nociception and inflammation, highlighting the need for further investigation in neural–immune communication in cancer pain.

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Tumor necrosis factor alpha secreted from oral squamous cell carcinoma contributes to cancer pain and associated inflammation

Abstract Patients with oral cancer report severe pain during function. Inflammation plays a role in the oral cancer microenvironment; however, the role of immune cells and associated secretion of inflammatory mediators in oral cancer pain has not been well defined. In this study, we used 2 oral cancer mouse models: a cell line supernatant injection model and the 4-nitroquinoline-1-oxide (4NQO) chemical carcinogenesis model. We used the 2 models to study changes in immune cell infiltrate and orofacial nociception associated with oral squamous cell carcinoma (oSCC). Oral cancer cell line supernatant inoculation and 4NQO-induced oSCC resulted in functional allodynia and neuronal sensitization of trigeminal tongue afferent neurons. Although the infiltration of immune cells is a prominent component of both oral cancer models, our use of immune-deficient mice demonstrated that oral cancer–induced nociception was not dependent on the inflammatory component. Furthermore, the inflammatory cytokine, tumor necrosis factor alpha (TNFα), was identified in high concentration in oral cancer cell line supernatant and in the tongue tissue of 4NQO-treated mice with oSCC. Inhibition of TNFα signaling abolished oral cancer cell line supernatant-evoked functional allodynia and disrupted T-cell infiltration. With these data, we identified TNFα as a prominent mediator in oral cancer–induced nociception and inflammation, highlighting the need for further investigation in neural–immune communication in cancer pain.

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Effects of a psychosocial intervention programme combined with exercise in community-dwelling older adults with chronic pain: A randomized controlled trial

Abstract

Background

Although researchers have recommended exercise training and psychosocial intervention to manage chronic pain, an effective intervention for Japanese community-dwelling older adults with chronic pain has not been established. This randomized controlled trial examined whether exercise training combined with psychosocial intervention more effectively improves pain, psychological status and physical activity than does exercise training alone in this population.

Methods

We randomized 128 older adults with chronic pain to either an intervention group (n = 64) involving exercise training combined with psychosocial intervention, or a control group (n = 64) involving only exercise training. Exercise training comprised weekly 60-min sessions for 12 weeks. Psychosocial intervention involved changing participants' focus on pain using self-management education and cognitive behavioural therapy, and participants recorded their daily pain intensity and step counts. Pain intensity, psychological status and physical activity were assessed before and 12 weeks after the intervention.

Results

A time-by-group interaction emerged for psychological status (p = 0.003) and physical activity (p < 0.001), both favouring the intervention group. The intervention group also showed greater improvement in pain intensity at 12 weeks than did the control group (p = 0.007).

Conclusions

Exercise training combined with psychosocial intervention improves key outcome indicators more effectively than does exercise training alone in older adults with chronic pain.

Significance

Although research has shown that combined exercise and psychosocial intervention is optimal for managing chronic pain, our study is the first, to the best of our knowledge, to test a specific intervention of this type in community-dwelling older adults with chronic pain in Japan.

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Relationship between self-reported cognitive difficulties, objective neuropsychological test performance and psychological distress in chronic pain

Abstract

Background

Persons with chronic pain often report problems with cognitive abilities, such as memory or attention. There is limited understanding of whether objective performance is consistent with subjective reports, and how psychological factors contribute. We aimed to investigate these relationships in a group of patients expressing cognitive concerns, and evaluate the utility of self-report tools for pain management settings.

Method

Participants with chronic pain (n = 41) completed standardized neuropsychological tests, and self-report measures of cognitive functioning, pain, mood and sleep, as part of a broader study investigating cognitive performance in pain.

Results

Average neuropsychological test performance was subtly below normative means (within one standard deviation). Twenty-five percent of the sample scored substantially below age-adjusted norms on one or more objective tests. There were moderate-to-large associations between objective performance (e.g. Trail-Making B) and subjective cognitive complaints (e.g. Everyday Memory Questionnaire – Revised), controlling for age and education level. This was moderated by anxiety, such that subjective–objective relationships were particularly strong in those with higher anxiety. Poorer test performance was associated with higher pain intensity and catastrophizing. Subjective–objective cognition relationships remained after controlling for catastrophizing.

Conclusion

Patients’ self-reported cognitive concerns concurred with objectively measured performance, independent of age, education and catastrophizing. Moreover, those with severe anxiety were more accurate in predicting their cognitive performance. The findings highlight some interesting cognition–mood relationships, and suggest that easy-to-administer questionnaires, such as the Everyday Memory Questionnaire – Revised and the Behavior Rating Inventory of Executive Function – Adult Version, may be useful to capture cognitive concerns in clinical settings.

Significance

Cognitive concerns in chronic pain reflected objective neurocognitive performance. This was moderated by anxiety, such that self-reported cognition was more consistent with objective performance in those with high anxiety. Our findings suggest that reported cognitive concerns should be heeded, and self-report measures may be used clinically to facilitate dialogue about cognitive functioning.

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Current evidence of cannabinoid-based analgesia obtained in preclinical and human experimental settings

Abstract

Cannabinoids have a long record of recreational and medical use and become increasingly approved for pain therapy. This development is based on preclinical and human experimental research summarized in this review. Cannabinoid CB₁ receptors are widely expressed throughout the nociceptive system. Their activation by endogenous or exogenous cannabinoids modulates the release of neurotransmitters. This is reflected in antinociceptive effects of cannabinoids in preclinical models of inflammatory, cancer and neuropathic pain, and by nociceptive hypersensitivity of cannabinoid receptor-deficient mice. Cannabis-based medications available for humans mainly comprise Δ⁹-tetrahydrocannabinol (THC), cannabidiol (CBD) and nabilone. During the last 10 years, six controlled studies assessing analgesic effects of cannabinoid-based drugs in human experimental settings were reported. An effect on nociceptive processing could be translated to the human setting in functional magnetic resonance imaging studies that pointed at a reduced connectivity within the pain matrix of the brain. However, cannabinoid-based drugs heterogeneously influenced the perception of experimentally induced pain including a reduction in only the affective but not the sensory perception of pain, only moderate analgesic effects, or occasional hyperalgesic effects. This extends to the clinical setting. While controlled studies showed a lack of robust analgesic effects, cannabis was nearly always associated with analgesia in open-label or retrospective reports, possibly indicating an effect on well-being or mood, rather than on sensory pain. Thus, while preclinical evidence supports cannabinoid-based analgesics, human evidence presently provides only reluctant support for a broad clinical use of cannabinoid-based medications in pain therapy.

Significance

Cannabinoids consistently produced antinociceptive effects in preclinical models, whereas they heterogeneously influenced the perception of experimentally induced pain in humans and did not provide robust clinical analgesia, which jeopardizes the translation of preclinical research on cannabinoid-mediated antinociception into the human setting.

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Central sensitization: Nice to know?

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Tactile acuity is reduced in people with chronic neck pain

Tactile acuity deficits have been demonstrated in a range of persistent pain conditions and may reflect underlying cortical re-organisation.

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Decompression surgery fails to relieve shoulder impingement in trial

Decompression surgery does not significantly reduce symptoms in patients with subacromial shoulder pain, show the results of a randomised trial to assess this common surgical procedure.1“Our findings...

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Do Correlates of Pain-Related Stoicism and Cautiousness Differ in Younger and Older People with Advanced Cancer?

• Younger and older patients displayed age-related correlates of stoicism/cautiousness• Activity engagement was the most common correlate for both age groups• Young patients' stoicism/cautiousness related to discomfort with dependence on others• Older patients' stoicism/cautiousness related to avoiding thoughts of stressful events• Lifespan developmental issues must be considered in models of cancer pain adaptation

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The swollen pinna

A 65 year old man presented to his general practitioner with a one month history of pain and swelling of his left ear. His only comorbidity was a renal transplant 14 years earlier for immunoglobulin...

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A man with knee pain after a fall

A 47 year old man presented with a painful swollen right knee after a fall down stairs. On examination, his right knee was swollen, and there was infrapatellar tenderness, a palpable defect inferior...

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