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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Wide-spread cultural beliefs influence personal experiences and clinical treatment of pain, yet are often unexamined and unchallenged in the pain literature. The common cultural belief that people generally over-report or exaggerate pain is familiar, reflected in discordant patient-provider pain assessments, and compounded in the context of disparities in pain treatment. However, no studies have directly measured the prevalence of this belief among the general population, nor challenged the validity of this assumption by assessing normative pain reporting in clinical settings. ⋯ Results reinforce the need for respecting patient pain reports, and suggest that distrust surrounding others' pain experiences is prevalent in society. PERSPECTIVE: Most people claim to report their pain as accurately as possible, while simultaneously perpetuating common cultural beliefs that others over-report their pain. This fundamental pain bias highlights a pervasive misconception that likely contributes to patient-provider mistrust and broader cultural pain stigma.
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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.