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Emerging information suggests a potential role of medicinal cannabis in pain medication in addition to enhancing immune functions. Endometriosis is a disease of women of reproductive age associated with infertility and reproductive failure as well as chronic pain of varying degrees depending on the stage of the disease. Currently, opioids are being preferred over nonsteroidal anti-inflammatory drugs (NSAID) due to the latter's side effects. However, as the opioids are becoming a source of addiction, additional pain medication is urgently needed. Cannabis offers an alternative therapy for treating the pain associated with endometriosis. Information on the use and effectiveness of cannabis against endometriotic pain is lacking. Moreover, expression of receptors for endocannabinoids by the ovarian endometriotic lesions is not known. The goal of this study was to examine whether cannabinoid receptors 1 and 2 (CB1 and CB2) are expressed by ovarian endometriotic lesions. Archived normal ovarian tissues, ovaries with endometriotic lesions, and normal endometrial tissues were examined for the presence of endometrial stromal cells using CD10 (a marker of endometrial stromal cells). Expression of CB1 and CB2 were determined by immunohistochemistry, immunoblotting, and gene expression studies. Intense expression for CB1 and CB2 was detected in the epithelial cells in ovarian endometriotic lesions. Compared with stroma in ovaries with endometriotic lesions, the expression of CB1 and CB2 was significantly higher in the epithelial cells in endometriotic lesions in the ovary ( < 0.0001 and < 0.05, respectively). Immunoblotting and gene expression assays showed similar patterns for CB1 and CB2 protein and (gene encoding CB1) and (gene encoding CB2) gene expression. These results suggest that ovarian endometriotic lesions express CB1 and CB2 receptors, and these lesions may respond to cannabinoids as pain medication. These results will form a foundation for a clinical study with larger cohorts.
Learn More >To investigate the prevalence of neuropathic pain symptoms and to analyze the correlation between neuropathic symptoms with pain-related, psychological, and cognitive variables in COVID-19 survivors exhibiting "de novo" post-COVID pain.
Learn More >Pain is often viewed and studied as an isolated perception. However, cognition, emotion, salience effects, and autonomic and sensory input are all integrated to create a comprehensive experience. Music-induced analgesia has been used for thousands of years, with moderate behavioural effects on pain perception, yet the neural mechanisms remain ambiguous. The purpose of this study was to investigate the effects of music analgesia through individual ratings of pain, and changes in connectivity across a network of regions spanning the brain and brainstem that are involved in limbic, paralimbic, autonomic, cognitive, and sensory domains. This is the first study of its kind to assess the effects of music analgesia using complex network analyses in the human brain and brainstem. Functional MRI data were collected from 20 healthy men and women with concurrent presentation of noxious stimulation and music, in addition to control runs without music. Ratings of peak pain intensity and unpleasantness were collected for each run and were analysed in relation to the functional data. We found that music alters connectivity across these neural networks between regions such as the insula, thalamus, hypothalamus, amygdala and hippocampus (among others), and is impacted by individual pain sensitivity. While these differences are important for how we understand pain and analgesia, it is essential to note that these effects are variable across participants and provide moderate pain relief at best. Therefore, a therapeutic strategy involving music should use it as an adjunct to pain management in combination with healthy lifestyle changes and/or pharmaceutical intervention.
Learn More >The trigeminal ganglion (TG) is the primary site of aberration in trigeminal neuralgia (TN), and hence a crucial site where afferent input can be modulated. Here, we postulated that inhibiting TG optogenetics using flexible optic cannula would diminish brainstem trigeminal nucleus caudalis (TNC) neuronal activity and pain behavior in TN rat model. Infraorbital nerve constriction was employed to induce TN in female Sprague-Dawley rats, while naive and sham rats served as controls. TG-directed microinjections of AAV virus containing either the optogenetic or null vector were delivered to rats in each group. electrophysiological responses were obtained from the ventral posteromedial nucleus (VPm) of the thalamus with simultaneous TG optogenetic stimulation using flexible optic cannula as well the effects on behavioral responses were investigated. Recordings in TN rats revealed a decrease in burst firing activity during yellow laser driven inhibition on TG, as well as considerably improved behavioral responses. In contrast, we noticed persistent hypersensitivity and increased tonic firing with blue laser stimulation which indicates that TG inhibition can synchronize trigeminal pain signal transmission in a TN animal model. The potential of an optogenetic approach in TG itself with flexible optic fiber to directly disrupt the trigeminal pain circuitry delivers fundamental underpinnings toward its prospective as a trigeminal neuralgia management.
Learn More >Induced pluripotent stem cells (iPS-cells) have significantly expanded our experimental possibilities, by creating new strategies for the molecular study of human disease and drug development. Treatment of pain has not seen much improvement over the past decade, likely due to species differences in preclinical models. Thus, iPS-cell derived sensory neurons offer a highly welcome translational approach for research and drug development. Although central neuronal differentiation is relatively straightforward, the successful and reliable generation of peripheral neurons requires more complex measures. Here, we describe a small molecule-based protocol for the differentiation of human sensory neurons from iPS-cells which renders functional nociceptor-like cells within several weeks.
Learn More >Given the relatively high rates of suicidal ideation and attempt among people with chronic pain, there is a need to understand the underlying factors to target suicide prevention efforts. To date, no study has examined the association between pain phenotypes and suicide related behaviors among those with mild traumatic brain injuries.
Learn More >Music interventions accommodate the profound need for non-pharmacological pain treatment. The analgesic effect of listening to music has been widely demonstrated across studies. Yet, the specific mechanisms of action have still to be elucidated. Although the endogenous opioid and dopamine systems have been suggested to play an important role, a direct link has not been established. In addition, the involvement of placebo mechanisms is likely while largely unexplored. We examined the analgesic effect of music in healthy participants ( = 48) using a 3 × 3 within-subjects design with pharmacological manipulations and a matched, auditory control for music. Participants were exposed to thermal pain stimuli while listening to three auditory excerpts: music (active condition), nature sound (matched, auditory contextual condition), and noise (neutral control condition). The participants rated their expected and perceived pain levels in relation to each of the auditory excerpts. To investigate the involvement of the endogenous opioid and dopamine systems, the test session was performed three times on separate days featuring a double-blind randomized oral administration of naltrexone (opioid antagonist), haloperidol (dopamine antagonist), and an inactive agent (control). Our results support an analgesic effect of music. Contrary to current hypotheses, neither of the antagonists attenuated the effect of music. Yet, the participants' expectations for pain relief predicted their perceived pain levels during the auditory excerpts-even when controlling for a gradual learning effect. In conclusion, we demonstrate that the analgesic effect of music is at least partially mediated by expectations of an analgesic effect-a core mechanism in placebo effects-but not by opioid and dopamine-dependent mechanisms.
Learn More >COVID-19 pandemic containment measures have led to changes in various areas of life, including restrictions on health care. Patients with chronic pain may have faced an increased burden during pandemic and the resources of this vulnerable population are unknown. Therefore, a qualitative study was conducted to understand how people with chronic pain have experienced the course of the pandemic.
Learn More >Complex regional pain syndrome (CRPS) is usually triggered by trauma or a surgical procedure, and it typically becomes an established one after an intense inflammatory process with chronic pain and edema as the main symptoms. Available treatments for CRPS have low efficacy. This study aimed to evaluate the clinical and immunoregulatory effects of omega-3 polyunsaturated fatty acid (PUFA) supplementation on paw edema and anti- and pro-inflammatory cytokines and macrophage phenotypes in the chronic post-ischemia pain (CPIP) preclinical model of CRPS-Type I.
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