Browse by Audience
Basic pain research has shed light on key cellular and molecular mechanisms underlying nociceptive and phenomenological aspects of pain. Despite these advances, [[we still yearn for] the discovery of novel therapeutic strategies to address the unmet needs of about 70% of chronic neuropathic pain patients whose pain fails to respond to opioids as well as to other conventional analgesic agents. Importantly, a substantial body of clinical observations over the past decade cumulatively suggests that the psychedelic class of drugs may possess heuristic value for understanding and treating chronic pain conditions. The present review presents a theoretical framework for hitherto insufficiently understood neuroscience-based mechanisms of psychedelics' potential analgesic effects. To that end, searches of PubMed-indexed journals were performed using the following Medical Subject Headings' terms: pain, analgesia, inflammatory, brain connectivity, ketamine, psilocybin, functional imaging, and dendrites. Recursive sets of scientific and clinical evidence extracted from this literature review were summarized within the following key areas: (1) studies employing psychedelics for alleviation of physical and emotional pain; (2) potential neuro-restorative effects of psychedelics to remediate the impaired connectivity underlying the dissociation between pain-related conscious states/cognitions and the subcortical activity/function leading to the eventual chronicity through immediate and long-term effects on dentritic plasticity; (3) anti-neuroinflammatory and pro-immunomodulatory actions of psychedelics as the may pertain to the role of these factors in the pathogenesis of neuropathic pain; (4) safety, legal, and ethical consideration inherent in psychedelics' pharmacotherapy. In addition to direct beneficial effects in terms of reduction of pain and suffering, psychedelics' inclusion in the analgesic armamentarium will contribute to deeper and more sophisticated insights not only into pain syndromes but also into frequently comorbid psychiatric condition associated with emotional pain, e.g., depressive and anxiety disorders. Further inquiry is clearly warranted into the above areas that have potential to evolve into further elucidate the mechanisms of chronic pain and affective disorders, and lead to the development of innovative, safe, and more efficacious neurobiologically-based therapeutic approaches.
Learn More >Primary sensory neurons in dorsal root ganglia (DRG) are wrapped by satellite glial cells (SGCs), and neuron-SGC interaction may affect somatosensation, especially nociceptive transmission. P2-purinergic receptors (P2Rs) are key elements in the two-way interactions between DRG neurons and SGCs. However, because the cell types are in such close proximity, conventional approaches such as in vitro culture and electrophysiologic recordings are not adequate to investigate the physiologically relevant responses of these cells at a population level. Here, we performed in vivo calcium imaging to survey the activation of hundreds of DRG neurons in Pirt-GCaMP6s mice and to assess SGC activation in GFAP-GCaMP6s mice in situ. By combining pharmacologic and electrophysiologic techniques, we investigated how ganglionic purinergic signaling initiated by α,β-methyleneadenosine 5'-triphosphate (α,β-MeATP) modulates neuronal activity and excitability at a population level. We found that α,β-MeATP induced robust activation of small neurons-likely nociceptors-through activation of P2X3R. Large neurons, which are likely non-nociceptive, were also activated by α,β-MeATP, but with a delay. Blocking pannexin 1 channels attenuated the late phase response of DRG neurons, indicating that P2R stimulation may subsequently induce paracrine ATP release, which could further activate cells in the ganglion. Moreover, ganglionic α,β-MeATP treatment in vivo sensitized small neurons and enhanced responses of spinal wide-dynamic-range neurons to subsequent C-fiber inputs, suggesting that modulation via ganglionic P2R signaling could significantly affect nociceptive neuron excitability and pain transmission. Therefore, targeting functional P2Rs within ganglia may represent an important new strategy for pain modulation.
Learn More >The experience of pain and pain behaviors is not only determined by physiological but also psychosocial factors. In this context, the learning history of the individual and specifically operant reinforcement related to spouse responses might play an important role. We investigated the effect of a solicitous and habitually pain-reinforcing spouse for the processing of pain in patients with chronic pain. Using multichannel electroencephalography, pain behaviors, and self-reports of pain, we examined 20 patients with chronic back pain (10 with solicitous and 10 with nonsolicitous spouses) and 10 matched healthy controls. The participants received a series of painful and nonpainful electrical stimuli applied to the site of pain (back) and a control area (finger) in the presence vs absence of the spouse. The global field power of the electroencephalogram with a focus in the frontal region was enhanced in patients with chronic back pain who had a solicitous spouse compared to those with a nonsolicitous spouse and the healthy controls. This was specific for the painful stimulation at the back and occurred only in the presence but not the absence of the spouse. Pain ratings of intensity and unpleasantness were also higher in the patients with solicitous spouses when the spouse was present during painful stimulation. These data suggest that significant other responses indicative of operant reinforcement may have a direct effect on the cerebral processing of pain and related pain perception.
Learn More >Most ocular diseases are associated with pain. While pain has been generally considered a mere (deleterious) additional symptom, it is now emerging that it is a key modulator of innate/adaptive immunity. Because the cornea receives the highest nerve density of the entire body, it is an ideal site to demonstrate interactions between pain and the immune response. Indeed, most neuropeptides involved in pain generation are also potent regulators of innate and adaptive leukocyte physiology. On the other hand, most inflammatory cells can modulate the generation of ocular pain through release of specific mediators (cytokines, chemokines, growth factors, lipid mediators). This review will discuss the reciprocal role(s) of ocular surface (and specifically: corneal) pain on the immune response of the eye. Finally, we will discuss clinical implications of such reciprocal interactions in the context of highly prevalent corneal diseases.
Learn More >Spinal cord stimulation (SCS) has been shown to reduce opioid consumption, reduce pain, improve quality of life compared to conventional therapy, and be more effective than spine reoperation in carefully selected patients. In this study, we evaluate readmissions after SCS implantation procedures, costs, predictors, and etiologies for readmission following implantation procedures.
Learn More >Headache has a variety of types, such as episodic primary headaches (EPH) and chronic primary headache (CPH) in its primary form. There is a positive correlation between these two types of headaches and hypertension (HTN), but in some works this correlation has been reported negatively. Therefore, we planned to study HTN-CPH as well as HTN-EPH correlation in our population. A sample of Rafsanjan population (10,000 individuals) entered the cohort study, as one of the Prospective Epidemiological Research Studies in Iran (PERSIAN). We compared the frequency of HTN categories in CPH and EPH cases with a normal population. Out of 9933 participants (46.6% males and 53.4% females) about 29% had EPH and 7.5% had CPH. HTN was found in 24.27% of EPH cases and 31.98% of CPH cases. HTN was also found to be associated with EPH and CPH in the crude model. Two Categories of HTN (Long controlled and uncontrolled) were not associated with EPH. On the other hand, CPH showed associations with all of the HTN categories. After included all variables and confounders, EPH and CPH had association with HTN without any considerable changes. There is strong HTN-EPH as well as HTN-CPH correlations in the studied population.
Learn More >Clinical trial populations may not reflect clinical practice: knowledge generated in other settings can inform clinical decision-making.
Learn More >Anger is a negative emotion characterized by antagonism toward someone or something, is rooted in an appraisal or attribution of wrongdoing, and is accompanied by an action tendency to undo the wrongdoing. Anger is prevalent in individuals with chronic pain, especially those with chronic primary pain. The associations between anger and pain-related outcomes (e.g., pain intensity, disability) have been examined in previous studies. However, to our knowledge, no systematic review or meta-analysis has summarized the findings of anger-pain associations through a focus on chronic primary pain. Hence, we sought to summarize the findings on the associations of anger-related variables with pain and disability in individuals with chronic primary pain.
Learn More >Study TR03 evaluated the safety and efficacy of nalbuphine ER for prurigo nodularis (PN) (NCT02174419).
Learn More >Chronic pain is one of the most common reasons adults seek medical care in the US, with prevalence estimates ranging from 11% to 40%. Mindfulness meditation has been associated with significant improvements in pain, depression, physical and mental health, sleep, and overall quality of life. Group medical visits are increasingly common and are effective at treating myriad illnesses, including chronic pain. Integrative Medical Group Visits (IMGV) combine mindfulness techniques, evidence based integrative medicine, and medical group visits and can be used as adjuncts to medications, particularly in diverse underserved populations with limited access to non-pharmacological therapies.
Learn More >