Pain
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The neural mechanisms of the affective-motivational symptoms of chronic pain are poorly understood. In chronic pain, our innate coping mechanisms fail to provide relief. Hence, these behaviors are manifested at higher frequencies. ⋯ We anatomically traced the postsynaptic targets of the spinal cord and LHA in the LPBN and found that they synapse onto overlapping populations. Activation of this LPBN population was sufficient to promote licking due to cold allodynia. In sum, our data indicate that the nociceptive inputs from the spinal cord and information on brain states from the hypothalamus impinge on overlapping LPBN populations to modulate their activity and, in turn, regulate the elevated affective-motivational responses in CIPN.
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There is growing acceptance for combining complementary and integrative health (CIH) therapies with standard rehabilitative care (SRC) for chronic pain management, yet little evidence on the best sequence of therapies. We investigated whether starting with CIH therapies or SRC is more effective in reducing pain impact. Participants were 280 service members with predominantly (88%) musculoskeletal chronic pain referred to an interdisciplinary pain management center who were randomized to a twice weekly program of either CIH therapies (n = 140) or SRC (n = 140) for the 3-week first stage of treatment. ⋯ At end of stage 1, pain impact decreased significantly more in the CIH group (29.8 points [SD 7.2] at baseline to 26.3 points [SD 7.9], change of -3.3 points [95% confidence interval, -4.2 to -2.5]) than in the SRC group (30.8 [SD 7.6] to 29.4 [SD 7.8], change of -0.9 points [95% confidence interval, -1.8 to -0.1]; P < 0.001). No significant between-group differences were observed after 6 weeks of treatment nor at 3- or 6-month follow-ups. Complementary and integrative health therapies may provide earlier improvement in pain impact than SRC, but this difference is not sustained.
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Pain clinical trials are notoriously complex and often inefficient in demonstrating efficacy, even for known efficacious treatments. A major issue is the difficulty in the a priori identification of specific phenotypes to include in the study population. Recent work has identified the extent of widespread pain as an important determinant of the likelihood of response to therapy, but it has not been tested in clinical trials for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). ⋯ Participants with predominately local pain (ie, limited widespread pain symptoms) responded to therapy targeting local symptoms, whereas those with widespread pain did not. Alternatively, participants with widespread pain beyond their local pelvic pain responded to more centrally acting treatments. Our results suggest that differentiating patients based on widespread vs more localized pain is a key consideration for designing future clinical trials for conditions with variable pain profiles, such as IC/BPS and potentially other pain-based syndromic disorders.
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Many medications commonly used to treat neuropathic pain are associated with significant, dose-limiting adverse effects, including sedation, dizziness, and fatigue. These adverse effects are due to the activity of these medications within the central nervous system. The objective of this work was to investigate the interactions between peripherally restricted cannabinoid receptor and mu-opioid receptor (MOR) agonists on ongoing and evoked neuropathic pain behaviors in mouse models. ⋯ Importantly, combination dosing of these agents does not cause any detectable preferential behaviors or motor impairment. However, repeated dosing of these agents is associated with the development of tolerance to these drugs. Collectively, these findings suggest that leveraging synergistic pain inhibition between cannabinoid receptor and MOR agonists in peripheral sensory neurons may be worth examining in patients with neuropathic pain.