Articles: neuropathic-pain.
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Pain is a distressing sensation, resulting from real or potential tissue damage. It is crucial to protect our body, but it can be so intense that it requires treatment. Furthermore, in some circumstances, pain can become persistent/chronic, such as that triggered by inflammatory disease or neuropathy. ⋯ In this context, there is emerging evidence indicating that C5a, a component of the complement system, and its cell membrane receptor, C5aR, play a critical role in the genesis of acute and chronic pain states. Thus, this review will describe the mechanisms by which C5a/C5aR signaling participates in the cascade of events involved in the pathophysiology of acute (postoperative), inflammatory and neuropathic pain states. Furthermore, it will also highlight the current possibilities for the development of a novel class of analgesic drugs that target C5a/C5aR signaling.
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This double-blind randomized controlled study was designed to evaluate the analgesic effects of topical treatments with clonidine (CLON) and pentoxifylline (PTX) tested alone or as low- and high-dose combinations in a human experimental model of pain. Of 69 healthy subjects aged 18 to 60 years, 23 each were randomly allocated to low-dose (0.04% + 2%) and high-dose (0.1% + 5%) CLON + PTX groups. Both of these groups also received their corresponding placebos in one of 2 treatment periods separated by at least 48 hours. ⋯ Importantly, the high-dose combination produced lower VAS ratings than CLON alone, which were lower than PTX alone. Results also revealed significant inhibition of postcapsaicin dynamic mechanical allodynia and PMA for the high-dose combination compared with placebo, and of PMA for CLON compared with the low-dose combination. Hence, the present data are supportive of further clinical investigation of the high-dose topical combination of CLON + PTX in complex regional pain syndrome and neuropathic pain patients, for which our preclinical data predict efficacy.
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Repetitive transcranial magnetic stimulation (rTMS) can relieve neuropathic pain when applied at high frequency (HF: 5-20 Hz) over the primary motor cortex (M1), contralateral to pain side. In most studies, rTMS is delivered over the hand motor hot spot (hMHS), whatever pain location. Navigation systems have been developed to guide rTMS targeting, but their value to improve rTMS efficacy remains to be demonstrated. ⋯ Navigation may improve HF-rTMS efficacy in patients with limb pain, whereas targeting remains to be optimized for more diffuse or facial pain. WHAT DOES THIS STUDY ADD?: To produce analgesic effects, HF-rTMS should be applied over the precentral cortex contralaterally to the painful side. Although the hMHS is the target normally chosen for stimulation, the optimal target has not been defined yet. Neuronavigational methods have been recently developed; they allow the integration of MRI data and are thought to improve rTMS efficacy.
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Neuropathic pain, is caused by damage or disease affecting the somatosensory nervous system, leads to deterioration of the quality of life of patients. Most commonly, this deterioration is due to the inefficacy of treatment or to the adverse effects of systemic treatment. Pharmacotherapy of neuropathic pain involves the use of antiepileptic agents, antidepressants, and opioids that may lead to numerous adverse effects, particularly in elderly patients. Intravenous infusions of lidocaine may improve the efficacy of the analgesic treatment of neuropathic pain patients while not causing any significant adverse effects. ⋯ The best therapeutic effects of lidocaine infusion was observed in pain symptoms characterized by the highest intensity of baseline pain. Intravenous lidocaine administered at the dose of 5mg/kg of body weight over 30min is effective, safe and caused no significant adverse effects.
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Although conduction failure has been observed in nociceptive C-fibers, little is known regarding its significance or therapeutic potential. In a previous study, we demonstrated that C-fiber conduction failure, which is regarded as an intrinsic self-inhibition mechanism, was reduced in circumstances of painful diabetic neuropathy. In this study, we extend this finding in the complete Freund's adjuvant model of inflammatory pain and validate that the degree of conduction failure decreased and led to a greater amount of pain signals conveyed to the central nervous system. ⋯ ZD7288 promoted conduction failure by suppressing Ih as a mechanism to reduce the rising slope of the after-hyperpolarization potential. Moreover, perineuronal injection of ZD7288 inhibited abnormal mechanical allodynia and thermal hyperalgesia without affecting motor function or heart rate. Our data highlight the analgesic potential of local ZD7288 application and identify conduction failure as a novel target for analgesic therapeutic development.