The journal of pain : official journal of the American Pain Society
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Paclitaxel induces microglial activation and production of proinflammatory mediators in the dorsal horn, which contribute to the development and maintenance of central sensitization and pain behavior. MDA7, 1-([3-benzyl-3-methyl-2,3-dihydro-1-benzofuran-6-yl]carbonyl) piperidine, is a novel highly selective cannabinoid type 2 (CB2) agonist. We tested the hypothesis that activation of CB2 receptor by MDA7 modulates microglial dysregulation, suppresses the overexpression of brain-derived neurotrophic factor (BDNF) in microglia in the dorsal horn, and attenuates the central sensitization and pain behavior induced by paclitaxel. ⋯ Perspective: This study provides evidence that paclitaxel induced microglia dysregulation and epigenetically upregulated the microglial expression of BDNF, which led to sensitization of dorsal horn neurons and mechanical allodynia in rats. The CB2 agonist MDA7 alleviated these pathological processes. MDA7 represents an innovative therapeutic approach for treatment of chemotherapy-induced neuropathy.
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Review Meta Analysis
The blind leading the not so blind: a meta-analysis of blinding in pharmacological trials for chronic pain.
Patient blinding is a critical feature of double-blind placebo-controlled randomized controlled trials (RCTs). Yet, very little is known about practices for assessing and reporting blinding in chronic pain trials. We examined the rates and predictors of assessing blinding and its success in pharmacological RCTs for chronic pain. ⋯ The results indicated that blinding is rarely assessed and often fails. Some study characteristics were associated with lower rates of assessing blinding and its success, for example, pharmaceutical sponsorship and side effects. Implications and recommendations for chronic pain RCTs are discussed.
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Recent research has revealed robust cross-sectional and prospective associations among perceived injustice, pain, disability, and depressive symptoms in patients with chronic pain. To date, research has proceeded from the assumption that perceived injustice arises as a consequence of debilitating injury or illness. However, it is possible that perceived injustice might have trait-like characteristics, persisting even in the absence of an injustice-related eliciting event. ⋯ The results of the present study suggest that individuals vary in their trait-like propensity to experience negative life events as unjust and that trait perceived injustice contributes to adverse pain outcomes. PERSPECTIVE: The present findings suggest that perceived injustice might reflect an enduring tendency to experience negative life events as unjust. The findings also suggest that trait perceived injustice is associated with higher ratings of pain intensity and anger and more pronounced displays of pain behavior.
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Central poststroke pain (CPSP) is a neuropathic pain syndrome arising after a lesion of the central nervous system owing to cerebrovascular insult. Impaired daily activities and reduced quality of life in people suffering from CPSP justify the need for improved treatment. The detailed mechanism of CPSP is not well understood, but central disinhibition has been suggested. ⋯ Moreover, compared with the current first-line drug gabapentin for central neuropathic pain, an early treatment of EET showed greater efficacy in the secondary prevention of CPSP. Taken together, this study provided a proof of concept that EETs may have anti-CPSP effect by reserving normal thalamic inhibition through AP-δGABAAR signaling. PERSPECTIVE: Agents targeting EETs may serve as potential therapeutic options for stroke, the use of which at the initial period could not only block further nerve damage but also prevent the occurrence of CPSP.
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A rat model of neuropathic pain at 6 weeks after spinal nerve ligation (SNL6w) exhibits both mechanical hypersensitivity and impaired noxious stimuli-induced analgesia (NSIA). Repeated treatment with antidepressants can produce antihypersensitivity and restore NSIA. To examine the involvement of a brain-derived neurotrophic factor-mediated mechanism, a tropomyosin receptor kinase B (TrkB) agonist, 7,8-dihydroxyflavone (DHF), was administered to SNL6w rats (5 mg/kg/d for 5 days). ⋯ PERSPECTIVE: This article demonstrates that repeated treatment with TrkB agonist, DHF, restored endogenous analgesia. Repeated amitriptyline treatment showed similar effect via TrkB-mediated mechanisms, and the effect may be independent from the effect of antihypersensitivity. This effect of TrkB activation is promising for patients with chronic pain with impaired descending inhibition.