The journal of pain : official journal of the American Pain Society
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The strong need for a new foundational molecular framework for human nervous system research at the nociceptive level is now matched by comprehensive and quantitative capabilities for analyzing nociceptive tissues such as pathologic peripheral tissue, damaged peripheral nerve, dorsal root ganglia, spinal cord, and brain, where possible. However, this idea must be matched by equally strong organization and infrastructures for multisite tissue recovery, molecular analyses, data sharing, and long-term archiving. Experience from other human tissue analysis projects shows that a decades-long activity may be expected, hence "Be in it for the long haul." While certain milestones can be met fairly quickly, others aimed at molecular and neuroanatomical characterization of chronic pain disorders will require the sustained attention of the groups involved. ⋯ PERSPECTIVE: A concerted effort is needed to build human nociceptive tissue banks for multi-omic research. In addition to collecting tissue, a careful characterization of pain problems from donors is essential, as is a parallel effort to assess their concurrent medical problems, medications, and the many variables of general human activity and lifestyle that can impact the results. Given the projected long time frame, in addition to maintaining funding, sustaining motivation and momentum are critical factors for success.
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Psychedelic substances have played important roles in diverse cultures, and ingesting various plant preparations to evoke altered states of consciousness has been described throughout recorded history. Accounts of the subjective effects of psychedelics typically focus on spiritual and mystical-type experiences, including feelings of unity, sacredness, and transcendence. Over the past 2 decades, there has been increasing interest in psychedelics as treatments for various medical disorders, including chronic pain. ⋯ Challenges in evaluating psychedelics as treatments for chronic pain include identifying neurobiologic and psychosocial mechanisms of action and determining which pain conditions to investigate. Truly informative proof-of-concept and confirmatory randomized clinical trials will require careful selection of control groups, efforts to minimize bias from unblinding, and attention to the roles of patient mental set and treatment setting. PERSPECTIVE: There is considerable promise for the use of psychedelic therapy for pain, but evidence-based recommendations for the design of future studies are needed to ensure that the results of this research are truly informative.
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Observational Study
Preoperative Predictors of Complex Regional Pain Syndrome Outcomes in the 6 Months Following Total Knee Arthroplasty.
This prospective observational study evaluated preoperative predictors of complex regional pain syndrome (CRPS) outcomes in the 6 months following total knee arthroplasty (TKA). Participants were n = 110 osteoarthritis patients (64.5% female) undergoing unilateral TKA with no prior CRPS history. Domains of negative affect (depression, anxiety, catastrophizing), pain (intensity, widespread pain, temporal summation of pain [TSP]), pain interference, sleep disturbance, and pro-inflammatory status (tumor necrosis factor-alpha [TNF-a]) were assessed preoperatively. ⋯ Preoperative negative affect is unlikely to directly influence long-term CRPS risk. PERSPECTIVE: This article identifies preoperative predictors of CRPS features at 6 months following total knee arthroplasty, including more widespread pain and higher pain intensity, temporal summation of pain, pain interference, and tumor necrosis factor-alpha levels. Findings suggest the importance of central sensitization and inflammatory mechanisms in CRPS risk following tissue trauma.
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People with chronic pain report experiencing stigma, but few studies have explored this in detail. This mixed-methods study aimed to investigate factors that contribute to chronic pain stigma, the effects of stigma, and to explore the stigma experiences of people with chronic pain. Participants were 215 adults with chronic pain who completed questionnaires assessing chronic pain stigma, opioid use, mental health conditions, pain, depression, disability and social support, and 179 also answered open-ended questions about stigma experiences. ⋯ This study demonstrates the negative influence of stigma and presents a novel integrated model of chronic pain stigma which may be used to develop interventions. PERSPECTIVE: This study demonstrates the contributors to, and negative effects of, stigma for people with chronic pain. It presents an integrated model which could guide strategies to reduce chronic pain stigma amongst health professionals and the public, and to reduce self-stigma amongst people with pain.
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Dexamethasone supplementation to local anesthetics prolongs its action, yet the underlying mechanism is unclear. Previous studies have reported that increased p-p38 mitogen-activated protein kinase (MAPK) in the dorsal root ganglia (DRG) is associated with pain-associated behavior and that nitric oxide (NO), which is known to be a pronociceptive substance, directly inhibits sciatic nerve conduction. Here, we investigated the temporal changes in the hyperalgesic effect and p-p38 MAPK and NO synthase (NOS) expression levels in the DRG when dexamethasone was added to ropivacaine used for a sciatic nerve block (SNB) in postoperative pain model mice. ⋯ These results suggest that dexamethasone supplementation to local anesthetics prolongs the analgesic effect by inhibiting nNOS activity. PERSPECTIVE: The current study revealed that dexamethasone supplementation to local anesthetics prolongs the analgesic effect by inhibiting the activity of neuronal NOS and that p-p38 MAPK may not be involved in this phenomenon. Our findings offer a new target for the discovery of long-acting local anesthetics.