Long-lasting neuropathic pain induced by brachial plexus injury in mice: Role triggered by the pro-inflammatory cytokine, tumour necrosis factor alpha.
Brachial plexus avulsion (BPA) resulted in a marked and long-lasting mechanical hypernociception (up to 80 days) in comparison to a sham-operated group, as assessed by Von Frey filaments, in both Swiss and C57/BL6 mice. In the tail-flick test, both Swiss and C57/BL6 mice submitted to BPA showed a significant thermal hypernociception, which persisted for 10 days. Both mechanical and thermal hypernociception following BPA were abolished in tumour necrosis factor alpha (TNFalpha) p55 receptor knockout mice. Moreover, the mechanical hypernociception caused by BPA was inhibited by the local application of the anti-TNFalpha (10 and 100 ng/site) antibody at the time of the surgery or by the intravenous administration (100 microg/kg) of this antibody at the time of the surgery or 4 days after the BPA. A similar inhibition of the mechanical hypernociception was observed when treating mice with the TNFalpha synthesis inhibitor thalidomide (50 mg/kg, s.c.), either at the time of the surgery or 4 days after. The results suggest that the persistent thermal, and especially the persistent mechanical, hypernociception observed following BPA in mice is largely dependent on the generation of TNFalpha. Based on these results, it is possible to suggest that therapeutic strategies for blocking TNFalpha could represent a valuable approach for the treatment of persistent neuropathic pain.
Quintão
Nara L M
NL
Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, 88049-900 Florianópolis, SC, Brazil.
Balz
Daniela
D
Santos
Adair R S
AR
Campos
Maria M
MM
Calixto
João B
JB
D000818:Animals; D020516:Brachial Plexus Neuropathies / Q000150:complications*; D005260:Female; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009437:Neuralgia / Q000209:etiology* / Q000378:metabolism*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000502:physiology; D011930:Reaction Time / Q000502:physiology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha