Decreasing sympathetic sprouting in pathologic sensory ganglia: a new mechanism for treating neuropathic pain using lidocaine.
Lidocaine brings relief to those suffering from certain neuropathic pain syndromes in humans and in animal models. Evidence suggests that some neuropathic pain behaviors are closely associated with extensive sprouting of noradrenergic sympathetic fibers in the dorsal root ganglia (DRG). Using immunohistochemistry, we examined lidocaine's effects on abnormal sprouting of sympathetic fibers in two animal models: rats with unilateral spinal nerve ligation (SNL) and rats with complete sciatic nerve transection (CSNT). For the first time, we have demonstrated that systemic lidocaine beginning at the time of surgery via an implanted osmotic pump remarkably reduces sympathetic sprouting (2-3 fold) (e.g. the density of sympathetic fibers and the number of DRG neurons surrounded by sympathetic fibers) in axotomized DRGs in SNL rats. The effects of systemic lidocaine lasted more than 7 days after the termination of lidocaine administration. Similar results were obtained after topical application of lidocaine to the nerve trunk to block abnormal discharges originating in the neuroma in CSNT rats. Results strongly suggest that sympathetic sprouting in pathologic DRG may be associated with abnormal spontaneous activity originating in the DRG or the injured axons (e.g. neuroma). This finding provides new insight into the mechanisms underlying sympathetic sprouting and increases our current understanding of the prolonged therapeutic effects of lidocaine on neuropathic pain syndromes.
Zhang
Jun-Ming
JM
Department of Anesthesiology, University of Arkansas for Medical Sciences, 4301 W. Markham St., #515, Little Rock, AR 72205, USA. zhangjunming@uams.edu
Li
Huiqing
H
Munir
Muhammad A
MA
D000320:Adrenergic Fibers / Q000187:drug effects*; D000779:Anesthetics, Local / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002452:Cell Count / Q000379:methods; D007839:Functional Laterality / Q000502:physiology; D017950:Ganglia, Sensory / Q000187:drug effects*; D007150:Immunohistochemistry / Q000379:methods; D008012:Lidocaine / Q000494:pharmacology / Q000627:therapeutic use*; D008026:Ligation / Q000379:methods; D009437:Neuralgia / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000293:injuries; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000779:Anesthetics, Local; D008012:Lidocaine; D014446:Tyrosine 3-Monooxygenase