Neuropathic pain consequent to peripheral injury is associated with local inflammation and overexpression of nitric oxide synthases (NOS) and inflammatory cytokines in locally recruited macrophages, Schwann and glial cells. We investigated the time course and localization of nitric oxide synthases (NOS) and cytokines in the central (spinal cord and thalamus) and peripheral nervous system (nerve and dorsal root ganglia), in a mouse model of mononeuropathy induced by sciatic nerve chronic constriction injury. ATP is recognized as an endogenous pain mediator. Therefore we also evaluated the role of purinergic signalling in pain hypersensitivity employing the P2 receptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), on pain behaviour, NOS and cytokines. The PPADS daily administration starting on day 3 after injury dose- and time-dependently decreased both tactile allodynia and thermal hyperalgesia. PPADS (25mg/kg) completely reversed nociceptive hypersensitivity and simultaneously reduced the increased NO/NOS system and IL-1beta in both peripheral (injured sciatic nerve and L4-L6 ipsilateral dorsal root ganglia) and central steps of nervous system (L4-L6 spinal cord and thalamus) involved in pain signalling. IL-6 was overexpressed only in the peripheral nervous system and PPADS prolonged administration reduced it in sciatic nerve. In conclusion, we hypothesize that NO/NOS and IL-1beta have a pronociceptive role in this neuropathy model, and that purinergic antagonism reduces pain hypersensitivity by inhibiting their overactivity.

Martucci, C., Trovato, A., Costa, B., Borsani, E., Franchi, S., Magnaghi, V., et al. (2008). The purinergic antagonist PPADS reduces pain related behaviours and interleukin-1beta, interleukin-6, iNOS and nNOS overproduction in central and peripheral nervous system after peripheral neuropathy in mice. PAIN, 137(1), 81-95 [10.1016/j.pain.2007.08.017].

The purinergic antagonist PPADS reduces pain related behaviours and interleukin-1beta, interleukin-6, iNOS and nNOS overproduction in central and peripheral nervous system after peripheral neuropathy in mice

COSTA, BARBARA SIMONA;
2008

Abstract

Neuropathic pain consequent to peripheral injury is associated with local inflammation and overexpression of nitric oxide synthases (NOS) and inflammatory cytokines in locally recruited macrophages, Schwann and glial cells. We investigated the time course and localization of nitric oxide synthases (NOS) and cytokines in the central (spinal cord and thalamus) and peripheral nervous system (nerve and dorsal root ganglia), in a mouse model of mononeuropathy induced by sciatic nerve chronic constriction injury. ATP is recognized as an endogenous pain mediator. Therefore we also evaluated the role of purinergic signalling in pain hypersensitivity employing the P2 receptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), on pain behaviour, NOS and cytokines. The PPADS daily administration starting on day 3 after injury dose- and time-dependently decreased both tactile allodynia and thermal hyperalgesia. PPADS (25mg/kg) completely reversed nociceptive hypersensitivity and simultaneously reduced the increased NO/NOS system and IL-1beta in both peripheral (injured sciatic nerve and L4-L6 ipsilateral dorsal root ganglia) and central steps of nervous system (L4-L6 spinal cord and thalamus) involved in pain signalling. IL-6 was overexpressed only in the peripheral nervous system and PPADS prolonged administration reduced it in sciatic nerve. In conclusion, we hypothesize that NO/NOS and IL-1beta have a pronociceptive role in this neuropathy model, and that purinergic antagonism reduces pain hypersensitivity by inhibiting their overactivity.
Articolo in rivista - Articolo scientifico
Scientifica
Neuropathic pain; Nitric oxide synthase; IL-1¿; IL-6; Purinergic antagonism; PPADS
English
81
95
Martucci, C., Trovato, A., Costa, B., Borsani, E., Franchi, S., Magnaghi, V., et al. (2008). The purinergic antagonist PPADS reduces pain related behaviours and interleukin-1beta, interleukin-6, iNOS and nNOS overproduction in central and peripheral nervous system after peripheral neuropathy in mice. PAIN, 137(1), 81-95 [10.1016/j.pain.2007.08.017].
Martucci, C; Trovato, A; Costa, B; Borsani, E; Franchi, S; Magnaghi, V; Panerai, A; Rodella, L; Valsecchi, A; Sacerdote, P; Colleoni, M
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/4159
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