Abstract
We determined the effect of N-acetylcysteine (NAC) on the expression of the phosphorylated p38 (p-p38) protein and superoxide anion generation (SAG), two important players in the processing of neuropathic pain, in the lumbosacral spinal cord of rats with chronic constriction injury (CCI)-induced neuropathic pain. The sciatic functional index (SFI) was also measured to assess the functional recovery post-nerve lesion. Thirty-six male Wistar rats were divided equally into the following groups: Naive (rats did not undergo surgical manipulation); Sham (rats in which all surgical procedures involved in CCI were used except the ligature), and CCI (rats in which four ligatures were tied loosely around the right common sciatic nerve), which received 2, 4, or 8 intraperitoneal injections of NAC (150 mg·kg-1·day-1) or saline beginning 4 h after CCI. Rats were sacrificed 1, 3, and 7 days after CCI. The SFI was measured on these days and the lumbosacral spinal cord was used for analysis of p-p38 expression and SAG. CCI induced a decrease in SFI as well as an increase in p-p38 expression and SAG in the spinal cord. The SFI showed a partial recovery at day 7 in saline-treated CCI rats, but recovery was improved in NAC-treated CCI rats. NAC induced a downregulation in p-p38 expression at all time-points evaluated, but did not reverse the increased SAG induced by CCI. Since p-p38 is a mediator in neuropathic pain and/or nerve regeneration, modulation of this protein may play a role in NAC-induced effects in CCI rats.
Highlights
Accumulating evidence suggests that the protein p38, a member of the family of mitogen-activated protein kinases (MAPK), contributes to neuropathic pain processing, as do nitric oxide (NO) and reactive oxygen species such as superoxide radicals [1,2,3,4]
Since NAC reacts relatively slowly with superoxide [5], and we were unable to find a report on the effect of NAC treatment on superoxide anion generation (SAG) in the spinal cord of rats with constriction injury (CCI), our study evaluated the effect of the Correspondence: A
The antinociceptive effect of the intraperitoneal administration of NAC is in line with a previous study that used rats submitted to CCI [6]
Summary
Accumulating evidence suggests that the protein p38, a member of the family of mitogen-activated protein kinases (MAPK), contributes to neuropathic pain processing, as do nitric oxide (NO) and reactive oxygen species such as superoxide radicals [1,2,3,4]. It was demonstrated that NAC treatment reduced NO metabolites in the lumbosacral spinal cord of CCI rats [6]. These authors suggested that the inhibition of the p38 protein might have contributed to this reduction in NO metabolites. Since MAPKs are activated by upstream kinases via phosphorylation [8], our study assessed the effect of intraperitoneal administration of NAC (150 mg Á kg–1 Á day–1), given for 1, 3, or 7 days, on the expression of the phosphorylated p38 (p-p38) protein in the lumbosacral spinal cord of rats with CCI. Analysis of the free walking pattern is a commonly used tool to assess the function of innervated target organs after nerve injury [9]
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