Pain
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Randomized Controlled Trial
Observing treatment outcomes in other patients can elicit augmented placebo effects on pain treatment: a double-blinded randomized clinical trial with patients with chronic low back pain.
Clinical research on social observational learning (SoL) as an underlying mechanism for inducing expectancy and eliciting analgesic placebo effects is lacking. This double-blinded randomized controlled clinical trial investigated the influence of SoL on medication-augmenting placebo effects in 44 patients with chronic low back pain. Our hypothesis was that observing positive drug effects on pain and mobility in another patient could increase pain reduction and functional capacity. ⋯ After the intervention, pain decreased in both groups (F [1, 41] = 7.16, P < 0.05, d = 0.83), with no difference between groups. However, the SoLG showed a significantly larger decrease in perceived disability (F [1, 41] = 5, P < 0.05, d = 0.63). The direct observation of patient with chronic low back pain of positive treatment outcomes in the sham patient seems to have enhanced the treatment effects while indirect verbal reports of reduced pain did not.
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Diabetic neuropathy, often associated with diabetes mellitus, is a painful condition with no known effective treatment except glycemic control. Studies with neuropathic pain models report alterations in cannabinoid and opioid receptor expression levels; receptors whose activation induces analgesia. We examined whether interactions between CB1R and opioid receptors could be targeted for the treatment of diabetic neuropathy. ⋯ Because the peptide endocannabinoid, hemopressin, caused a significant potentiation of MOR activity, we examined its effect on mechanical allodynia and found that it blocked allodynia in wild-type mice and mice with diabetic neuropathy lacking DOR (but have CB1R-MOR complexes). However, hemopressin does not alter the levels of CB1R-MOR complexes in diabetic mice lacking DOR but increases the levels of CB1R-DOR complexes in diabetic mice lacking MOR. Together, these results suggest the involvement of CB1R-MOR and CB1R-DOR complexes in diabetic neuropathy and that hemopressin could be developed as a potential therapeutic for the treatment of this painful condition.
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Mutations in the alpha subunit of voltage-gated sodium channel 1.7 (NaV1.7), encoded by SCN9A gene, play an important role in the regulation of nociception and can lead to a wide range of clinical outcomes, ranging from extreme pain syndromes to congenital inability to experience pain. To expand the phenotypic and genotypic spectrum of SCN9A-related channelopathies, we describe the proband, a daughter born from consanguineous parents, who had pain insensitivity, diminished temperature sensation, foot burns, and severe loss of nociceptive nerve fibers in the epidermis. Next-generation sequencing of SCN9A (NM_002977.3) revealed a novel homozygous substitution (c.377+7T>G) in the donor splice site of intron 3. ⋯ A functional study on proband RNA showed different aberrant transcripts, where exon 3 was missing and an intron fragment was included. A quantification study using real-time polymerase chain reaction showed a significant reduction of the NaV1.7 canonical transcript. Collectively, these data widen the spectrum of SCN9A-related insensitivity to pain by describing a mutation causing NaV1.7 deficiency, underlying the nociceptor dysfunction, and highlight the importance of molecular investigation of U12 introns' mutations despite the silent prediction.
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Neuropathic pain is a common condition experienced by older adults. Prevalence estimates of neuropathic pain and descriptive data of pharmacologic management among nursing home residents are unavailable. We estimated the prevalence of neuropathic pain diagnoses and described the use of pain medications among nursing home residents with possible neuropathic pain. ⋯ Resident characteristics associated with lack of medications included advanced age, dependency in activities of daily living, cognitive impairment, and diagnoses of comorbid conditions. A diagnosis of neuropathic pain is common among nursing home residents, yet many lack pharmacologic treatment for their pain. Future epidemiologic studies can help develop a more standard approach to identifying and managing neuropathic pain among nursing home residents.
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Pain is a common and debilitating symptom of inflammatory bowel disease (IBD). Based on evidence that peripheral GABAA receptor (GAR) inhibition plays an important role in establishing colonic afferent excitability and nociceptive threshold, we hypothesized that the increase in pain associated with IBD is due to, at least in part, a decrease in peripheral GAR-mediated inhibition. Acute colitis was induced with 5 days of dextran sodium sulfate (DSS, 3%) in the drinking water. ⋯ By contrast, at a concentration of gabazine that blocks only low-affinity GAR, there was no effect on the VMR in either DSS-treated or control mice, but at concentrations of the antagonist that block low-affinity and high-affinity GAR, the VMR was increased in control mice and decreased in DSS-treated mice. Furthermore, bicuculline increased the VMR in control mice but decreased it in DSS-treated mice. These data suggest that activating of low-affinity GAR or blocking high-affinity GAR may be effective therapeutic strategies for the management of pain in IBD.