Articles: hyperalgesia.
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Randomized Controlled Trial Clinical Trial
Mechanically induced axon reflex and hyperalgesia in human UV-B burn are reduced by systemic lidocaine.
The mechanisms for the induction of primary mechanical hyperalgesia are unclear. We analyzed the neurogenic axon reflex erythema (flare) following phasic mechanical stimulation in normal and in UV-B irradiated skin. In a cross-over double blind design (n = 10), low dose of systemic lidocaine suppressed mechanical hyperalgesia in sunburned skin and in the mechanically induced flare. ⋯ Systemic lidocaine suppressed the mechanically induced flare as well as the mechanical hyperalgesia in sunburned skin, while leaving the impact-induced ratings in normal skin unchanged. Systemic lidocaine reduced these effects of sensitization, but did not reduce ratings in normal skin. As mechanically insensitive ("sleeping") nociceptors have been shown to mediate the axon-reflex in human skin, sensitization of this class of nociceptors might contribute also to the UV-B-induced primary mechanical hyperalgesia.
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Systemic administration of local anesthetics has been shown to transiently reverse thermal and tactile hypersensitivity induced by peripheral nerve injury, effects that have been taken as suggesting direct actions on the peripheral nerves. The present study sought to determine whether a central site of action could contribute to, or account for, the effects of lidocaine on nerve injury-induced thermal and tactile hypersensitivity. Systemic lidocaine and its peripherally restricted analogues, QX-314 or QX-222, effectively reversed thermal hypersensitivity after spinal nerve ligation injury. Nerve injury-induced tactile hypersensitivity, however, was reversed by systemic lidocaine but not QX-314 or QX-222. Microinjection of either lidocaine or QX-314 into the rostral ventromedial medulla fully reversed spinal nerve ligation-induced thermal and tactile hypersensitivity. The data strongly suggest that nerve injury-induced thermal and tactile hypersensitivity are mediated through different mechanisms. In addition, the present study supports a prominent contribution of the central nervous system in the activity of systemically given lidocaine against nerve injury-induced tactile and thermal hypersensitivity. Thus, lidocaine might reverse tactile hypersensitivity mainly through its actions within the central nervous system, whereas its reversal of thermal hypersensitivity might occur through either central or peripheral sites. ⋯ Nerve injury-induced neuropathic pain has proved remarkably difficult to treat. Systemic administration of ion channel blockers such as lidocaine has been explored for the management of chronic pain. This work indicates that systemic rather than local administration of lidocaine would be more effective in treating tactile allodynia.
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Pharmacol. Biochem. Behav. · Jun 2004
Randomized Controlled Trial Comparative Study Clinical TrialLack of effect of two oral sodium channel antagonists, lamotrigine and 4030W92, on intradermal capsaicin-induced hyperalgesia model.
Preclinical studies have emphasized that persistent small afferent input will induce a state of central facilitation, which can be regulated by systemically administered sodium channel blockers. We have extended these preclinical studies to the human volunteers by examining the effects of lamotrigine and 4030W92, two structurally related voltage-sensitive sodium channel antagonists, on acute sensory thresholds and facilitated processing induced by intradermal capsaicin. Fifteen healthy subjects received 4030W92, lamotrigine, and placebo in a randomized order using double-blinded crossover design methodology in three sessions each separated by a 7-day washout period. ⋯ Similarly, oral lamotrigine or 4030W92 did not alter the pain scores reported from mechanical pain stimuli at any time postcapsaicin. This study showed a lack of effect of two structurally similar sodium channel antagonists on a human experimental pain model using intradermal capsaicin, which is consistent with other studies on the effects of sodium channel antagonists of capsaicin-induced pain and hyperalgesia. This lack of effect stands in contrast to reported effects of sodium channel antagonists on preclinical models of cutaneous hyperalgesia or effects of lamotrigine on clinical neuropathic pain.
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The disinhibition hypothesis of post-stroke central pain (CPSP) suggests that 'the excessive response (dysesthesia/hyperalgesia/allodynia) is accompanied by a em leader loss of sensation' resulting from a lesion of a 'lateral nucleus' of thalamus or of 'cortico-thalamic paths' [Brain 34 (1911) 102]. One recent elaboration of this hypothesis proposes a submodality specific relationship, such that injury to a cool-signaling lateral thalamic pathway disinhibits a nociceptive medial thalamic pathway, thereby producing both burning, cold, ongoing pain and cold allodynia. The current study quantitatively evaluated the sensory loss and sensory abnormalities to discern submodality relationships between these sensory features of CPSP. ⋯ The most dramatic case of cold allodynia occurred in a patient who had a normal detection threshold for cold. Individuals with cold hypoesthesia, strictly contralateral to the cerebro-vascular accident (CVA or stroke), were often characterized by the presence of burning, cold, ongoing pain, and by the absence, not the presence, of cold allodynia. Overall, these results in CPSP suggest that tactile allodynia occurs in disturbances of thermal/pain pathways that spare the tactile-signaling pathways, and that cold hypoesthesia is neither necessary nor sufficient for cold allodynia.
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We reported recently that redox agents, including the endogenous amino acid L-cysteine, modulate T-type Ca2+ currents in primary sensory neurons in vitro, and alter mechanical and thermal nociception in peripheral nociceptors in vivo in intact animals [Neuron 31 (2001) 75]. Here, we studied the effects of locally applied redox agents (L-cysteine and 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB) on thermal hyperalgesia in animals with neuropathic pain due to chronic constrictive injury (CCI) of the sciatic nerve. We found that, following injection into the peripheral receptive fields, the endogenous reducing agent L-cysteine increased thermal hyperalgesia in a dose-dependent manner in rats with CCI of the sciatic nerve as well as in sham-operated rats. ⋯ Mibefradil, a potent and preferential T-type Ca2+ channel blocker, abolished L-cysteine-induced increase in thermal hyperalgesia in both animal groups suggesting the involvement of T-type Ca2+ channels in peripheral nociception. These results indicate for the first time that redox modulation of T-type Ca2+ channels in rat peripheral nociceptors is operational in pain states caused by peripheral axonal injury. Since thermal hyperalgesia is a common symptom of axonal injury, locally applied oxidizing agents could be used as a novel treatment to ameliorate neuropathic pain.