Pain
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Chronic pain is associated with dysfunctional endogenous pain modulation, involving both central opioid and serotonergic (5-HT) signaling. Fibromyalgia (FM) is a chronic pain syndrome, characterized by widespread musculoskeletal pain and reduced exercise-induced hypoalgesia (EIH). In this study, we assessed the effects of 3 functional genetic polymorphisms on EIH in 130 patients with FM and 132 healthy controls. ⋯ Based on the proposed mechanisms of these genetic variants, the findings indicate antagonistic interactions between opioid and serotonergic mechanisms during EIH. Moreover, despite different baseline pain level, similar results were detected in FM and controls, not supporting an altered interaction between opioid and 5-HT mechanisms as the basis for dysfunction of EIH in patients with FM. In summary, our results suggest that, by genetic association, the mu-opioid receptor interacts with 2 major serotonergic structures involved in 5-HT reuptake and release, to modulate EIH.
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Medical cannabis (MC) is used for a variety of conditions including chronic pain. The goal of this report was to provide an in-depth qualitative exploration of patient perspectives on the strengths and limitations of MC. Members of MC dispensaries (N = 984) in New England including two-thirds with a history of chronic pain completed an online survey. ⋯ Analysis of answers to "What is it that you like most about MC?" (N = 2592 responses) identified 10 themes, including health benefits (36.0% of responses, eg, "Changes perception and experience of my chronic pain."), the product (14.2%, eg, "Knowing exactly what strain you are getting"), nonhealth benefits (14.1%), general considerations (10.3%), and medications (7.1%). Responses (N = 1678) to "What is it that you like least about MC?" identified 12 themes, including money (28.4%, eg, "The cost is expensive for someone on a fixed income"), effects (21.7%, eg, "The effects on my lungs"), the view of others (11.4%), access (8.2%), and method of administration (7.1%). These findings provide a patient-centered view on the advantages (eg, efficacy in pain treatment, reduced use of other medications) and disadvantages (eg, economic and stigma) of MC.
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Changes in chloride reversal potential in rat spinal cord neurons have previously been associated with persistent pain in nerve injury and inflammation models. These changes correlate with a decrease in the expression of the potassium chloride transporter, KCC2, and with increases in neuronal excitability. Here, we test the hypothesis that similar changes occur in mice with neuropathic pain induced by chronic constriction injury of the trigeminal infraorbital nerve (CCI-ION). ⋯ Quantitative real-time polymerase chain reaction analysis revealed no significant changes, at either 3 to 5 days or 12 to 14 days after CCI-ION, in either KCC2 or NKCC1. These findings suggest that CCI-ION in mice results in transient and modest changes in chloride reversal potentials, and that these changes may not persist during the late phase. This suggests that, in the mouse model of CCI-ION, chloride dysregulation may not have a prominent role in the central mechanisms leading to the maintenance of chronic pain.
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Approximately 7% to 10% of patients develop a chronic pain syndrome after stroke. This chronic pain condition is called central poststroke pain (CPSP). Recent studies have observed an abnormal increase in the secretion of brain-derived neurotrophic factor (BDNF) in spinal cord tissue after spinal cord injury. ⋯ Instead of being inhibited by the γ-aminobutyric acid (GABA) system in normal rats, multiunit activity in the MT was enhanced after a microinjection of muscimol, a GABAA receptor agonist, in CPSP animals. After CPSP, BDNF expression was enhanced in the MT, whereas the expression of GABAA channels and the cotransporter KCC2 decreased in the same area. These findings suggest that neuronal plasticity in the MT that was induced by BDNF overexpression after the thalamic lesion was a key factor in CPSP.