Articles: neuropathic-pain.
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High frequency spontaneous activity in injured primary afferents has been proposed as a pathological mechanism of neuropathic pain following nerve injury. Although spinal infusion of glial cell line-derived neurotrophic factor reduces the activity of injured myelinated A-fiber neurons after fifth lumbar (L5) spinal nerve ligation in rats, the implicated molecular mechanism remains undetermined. The fast-inactivating transient A-type potassium current (IA) is an important determinant of neuronal excitability, and five voltage-gated potassium channel (Kv) alpha-subunits, Kv1.4, Kv3.4, Kv4.1, Kv4.2, and Kv4.3, display IA in heterologous expression systems. ⋯ Among the examined Kv mRNAs, only the change in Kv4.1-expression was parallel with the change in IA after spinal nerve ligation and glial cell line-derived neurotrophic factor treatment. These findings suggest that glial cell line-derived neurotrophic factor should reduce the hyperexcitability of injured A-fiber primary afferents by IA recurrence. Among the five IA-related Kv channels, Kv4.1 should be a key channel, which account for this IA recurrence.
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Journal of pain research · Jan 2019
ReviewPharmacological rationale for tapentadol therapy: a review of new evidence.
Chronic pain could be considered as a neurological disorder. Therefore, appropriate selection of the therapy, which should consider the pathophysiological mechanisms of pain, can result in a successful analgesic outcome. Tapentadol is an analgesic drug which acts both as a μ-opioid receptor (MOR) agonist and as a noradrenaline reuptake inhibitor (NRI), thereby generating a synergistic action in terms of analgesic efficacy, but not for the burden of adverse effects. ⋯ This molecule holds the potential to address at least some of the current limitations of analgesic therapy due to its unique mechanism of action and has shown to be safe and effective in the treatment of chronic pain of cancer and noncancer etiologies including nociceptive, neuropathic and mixed pain. In particular, the MOR component of tapentadol activity predominantly allows for analgesia in nociceptive pain; on the other hand, the NRI component contributes, now in a predominant manner, for analgesic efficacy in cases of neuropathic pain states. This paper will discuss recent pieces of evidence on the pathophysiology of pain, the background on tapentadol and then present some new studies on how the unique mechanism of action of tapentadol provides a key role in its analgesic efficacy in a number of pain states and with a favorable safety profile.
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Restor. Neurol. Neurosci. · Jan 2019
Randomized Controlled TrialAnalgesia-enhancing effects of repetitive transcranial magnetic stimulation on neuropathic pain after spinal cord injury:An fNIRS study.
Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment for chronic intractable neuropathic pain in patients with spinal cord injury (SCI). However, the analgesia-enhancing effects of rTMS on conventional interventions (e.g., medications), and the underlying mechanisms remain poorly understood. ⋯ The findings of this preliminary study with a small patient sample suggest that the analgesia-enhancing effects of high-frequency rTMS might be related with the amelioration of M1 and PMC hypersensitivity, shedding light upon the clinical treatment of SCI-related neuropathic pain.
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Review
Non pharmacological treatment for neuropathic pain: Invasive and non-invasive cortical stimulation.
The use of medications in chronic neuropathic pain may be limited with regard to efficacy and tolerance. Therefore, non-pharmacological approaches, using electrical stimulation of the cortex has been proposed as an alternative. First, in the early nineties, surgically-implanted epidural motor cortex stimulation (EMCS) was proven to be effective to relieve refractory neuropathic pain. ⋯ The mechanism of action of tDCS differs from that of EMCS and rTMS, but the cortical target is the same, which is M1. Although the level of evidence of therapeutic efficacy in the context of neuropathic pain is lower for tDCS than for rTMS, interesting perspectives are opened by using at-home tDCS protocols for long-term management. Now, there is a scientific basis for recommending both EMCS and rTMS of M1 to treat refractory chronic neuropathic pain, but their application in clinical practice remains limited due to practical and regulatory issues.