Articles: neuropathic-pain.
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Postgraduate medicine · Apr 2022
ReviewNeuropharmacological basis for multimodal analgesia in chronic pain.
Managing chronic pain remains a major unmet clinical challenge. Patients can be treated with a range of interventions, but pharmacotherapy is the most common. These include opioids, antidepressants, calcium channel modulators, sodium channel blockers, and nonsteroidal anti-inflammatory drugs. ⋯ Ideally, combining drugs would produce synergistic action to maximize analgesia and reduce side effects, although sub-additive and additive analgesia is still advantageous if additive side-effects can be avoided. In this review, we discuss pain mechanisms, drug actions, and the rationale for mechanism-led treatment selection. Abbreviations: COX - cyclooxygenase, CGRP - calcitonin gene-related peptide, CPM - conditioned pain modulation, NGF - nerve growth factor, NNT - number needed to treat, NMDA - N-methyl-d-aspartate, NSAID - nonsteroidal anti-inflammatory drugs, TCA - tricyclic antidepressant, SNRI - serotonin-noradrenaline reuptake inhibitor, QST - quantitative sensory testing.
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T-type Ca2+ channels play a dual role in modulating the excitability of dorsal root ganglia neurons.
A subgroup of low-threshold dorsal root ganglia (DRG) neurons discharge action potentials (APs) with an afterdepolarizing potential (ADP). The ADP is formed by T-type Ca2+ currents. It is known that T-type Ca2+ currents contribute to neuropathic pain. ⋯ After injury, the proportion of DRG neurons with large T-type Ca2+ currents increased in parallel with the increase in the incidence of large-amplitude-ADP firing. And in addition to Cav3.2, Cav3.3 channels are also likely to contribute to low-threshold firing. The data revealed that T-type Ca2+ channels may play a dual role in modulating the injured neurons' high excitability through a cooperative process with Na+ channels, thereby contributing to neuropathic pain.
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Systemic administration of morphine increases serotonin (5-HT) in the spinal dorsal horn (SDH), which attenuates the analgesic effects of morphine on neuropathic pain through spinal 5-HT3 receptors. We hypothesized that dysfunction of the descending serotonergic system, including the periaqueductal gray (PAG), contributes to attenuate the efficacy of morphine on neuropathic pain through spinal 5-HT3 receptors and GABA neurons. Morphine (100 ng) injected into the PAG produced analgesic effects in normal rats, but not in spinal nerve ligation (SNL) rats. ⋯ Functional changes in GABAA receptors from inhibitory to facilitatory through the activation of TrkB receptors may contribute to the attenuated efficacy of morphine against neuropathic pain. PERSPECTIVE: Although morphine provides strong analgesia against acute pain, it has limited efficacy against neuropathic pain. This article demonstrates that functional changes in GABAA receptors in the spinal dorsal horn after nerve injury might strongly contribute to the attenuation of opioid-induced analgesia for neuropathic pain.
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Neuropathic pain (NP) is the cardinal symptom of neural injury, and its underlying molecular mechanism needs further investigation. Complements, especially complement 3 (C3), are involved in the pathophysiology of many neurological disorders, while the specific role of C3 in NP is still obscure. ⋯ Intrathecal injection of C3 antibody and C3aR antagonist alleviated NP in CCI model together with reduced M1 polarization of microglia. Our finding suggested that blockade of the C3/C3aR pathway might be a novel strategy for NP.
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The primary symptom of complex regional pain syndrome (CRPS) is pain. Interdisciplinary multimodal pain therapy (IMPT) is the gold standard of treatment. The purpose of this study was to identify the beneficial effect of inpatient IMPT on pain level, sensation, perception and impairment in patients with CRPS. ⋯ The current study demonstrated that IMPT has a highly beneficial effect on the level, experience and processing of pain in patients with CRPS.