Pain
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Multiple sclerosis (MS) is a neurodegenerative autoimmune disease with many known structural and functional changes in the central nervous system. A well-recognized, but poorly understood, complication of MS is chronic pain. Little is known regarding the influence of sex on the development and maintenance of MS-related pain. ⋯ We propose that tactile hypersensitivity in female EAE mice may be more immune-driven, whereas pain in male mice with EAE may rely more heavily on neurodegenerative and plasticity-related mechanisms. Morphological and inflammatory differences in the spinal cord associated with pain early in EAE progression supports the idea of differentially regulated pain pathways between the sexes. Results from this study may indicate future sex-specific targets that are worth investigating for their functional role in pain circuitry.
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The traditional translational approach in neuropathic pain research has mainly consisted to date in translating basic findings from animal models of nerve injury to the clinic. Because of the difficulty to extrapolate mechanisms from animals to humans, an inverse translational approach ("top-down") has been advocated and contributed to the development of therapy. ⋯ The biggest trend in recent translational research is to investigate mechanisms or predict therapeutic response in patients by integrating multimodal approaches. The present narrative review emphasizes these various aspects of translational research in neuropathic pain.
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Post-traumatic headache (PTH) is one of the most common, debilitating, and difficult symptoms to manage after a traumatic head injury. Although the mechanisms underlying PTH remain elusive, recent studies in rodent models suggest the potential involvement of calcitonin gene-related peptide (CGRP), a mediator of neurogenic inflammation, and the ensuing activation of meningeal mast cells (MCs), proalgesic resident immune cells that can lead to the activation of the headache pain pathway. Here, we investigated the relative contribution of MCs to the development of PTH-like pain behaviors in a model of mild closed-head injury (mCHI) in male rats. ⋯ Our data, however, also reveal that the development of latent sensitization, manifested as persistent hypersensitivity upon the recovery from mCHI-evoked acute cranial hyperalgesia to the headache trigger glyceryl trinitrate requires intact MC content during and immediately after mCHI. Collectively, our data implicate the acute activation of meningeal MCs as mediator of chronic pain hypersensitivity after a concussion or mCHI. Targeting MCs may be explored for early prophylactic treatment of PTH.
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Accumulating evidence has demonstrated that the enhanced synaptic plasticity of nociceptive interneurons in the spinal dorsal horn is the basis of central sensitization in neuropathic pain. Our previous results demonstrated that sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, alleviates neuropathic pain in type 2 diabetes mellitus rats. SIRT1 has also been reported to regulate synaptic plasticity in different brain neurons. ⋯ SIRT1-shRNA induced pain behavior and enhanced structural synaptic plasticity in normal rats and increased synapse-associated proteins levels in normal rats and spinal neurons. Intrathecal injection of AAV-Cre-EGFP into SIRT1 mice also induced pain behavior and enhanced synaptic plasticity of the spinal dorsal horn neurons. These results suggest that SIRT1 plays an important role in the progression of DNP by regulating synaptic plasticity of spinal dorsal horn neurons.
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Current guidelines for addressing opioid cessation in the context of chronic pain management recommend that opioids be discontinued if the risks outweigh the benefits. However, few studies have focused on understanding opioid cessation from the perspective of individuals with chronic pain. This mixed-method study included 49 former opioid users with chronic pain and used quantitative survey data and qualitative focus group data to identify themes pertaining to former opioid user's experience before, during, and after opioid cessation. ⋯ Half of the former opioid users reported their pain to be better or the same after stopping opioids; however, 47% of the sample reported feeling worse pain since stopping their opioids. As the pendulum swings from pain control to drug control, we must ensure that the response to the opioid epidemic does not cause harm to individuals with chronic pain. Novel opioid cessation interventions are needed in combination with methods of addressing individual challenges and barriers to adequate pain relief including access to and provision of nonopioid alternatives for pain management.