N-acetylcysteine downregulates phosphorylated p-38 expression but does not reverse the increased superoxide anion levels in the spinal cord of rats with neuropathic pain

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.

Research on the analgesic effect and mechanism of gabapentin on rats model with tibia metastatic cancer pain / 中国生化药物杂志

Objective To study the analgesic effect and mechanism of gabapentin on tibia metastatic cancer pain rat model constructed by walker-256 breast cancer cells.Methods 30 Female wistar rats were randomly divided into sham group,model group and GBP group(100 mg/kg),each group had 10 rats.Sham operation were used as operation control and tibia metastatic cancer pain operation were done separately.Paw withdrawal mechanical threshold and observation of X-ray were used to evaluate rats’pain behavior.ISCUS biochemical method,radioimmunoassay,and streaming multi-factor detection technique were used to detect glutamate level of cerebrospinal fluid,substance P level in the spinal cord and expression of IL-12P70,IFN-γ,β-NGF in the tumor tissue.Results Compared with sham group,paw withdrawal mechanical threshold of tibia metastatic rat model in operaion group were decreased significantly,and X-ray showed bone destruction,the glutamate level of cerebrospinal fluid and substance P level in the spinal cord were increased significantly(P<0.01 or P<0.05).IL-12P70 and IFN-γlevels were significantly lower andβ-NGF level was higher than that in sham group (P<0.05).Compared with model group,paw withdrawal mechanical threshold of rats in gabapentin group began to rise in 30 min after administration,and peaked in 60~300 min(P<0.01).Gabapentin reduced the glutamate level of cerebrospinal fluid,substance P level in the spinal cord andβ-NGF level of tumor tissue concentrations significantly(P<0.01 or P<0.05),but increased IL-12P70 and IFN-γlevels of tumor tissue.Conclusion Gabapentin can relieve the bone cancer pain of rat model.Its analgesic mechanism may lie indecreasing the levels of central excitatory amino acids,pain-associated neuromodulator and the nerve growth factor,and enhancing the peripheral immune function.

Melittin-induced Nociceptive Responses are Alleviated by Cyclooxygenase-1 Inhibitor

Melittin-induced pain model has been known to be very useful for the study of pain mechanism. Melittin-induced nociceptive responses are reported to be modulated by the changes in the activity of excitatory amino acid receptor, calcium channel, spinal serotonin receptor and extracellular signaling-regulated kinase. The present study was undertaken to investigate the role of cyclooxygenase (COX) in the melittin-induced nociception. Changes in mechanical threshold, flinchings and paw thickness were measured before and after intraplantar injection of melittin in the rat hind paw. Also studied were the effects of intraperitonealy administered diclofenac (25 mg & 50 mg/kg), piroxicam (10 mg & 20 mg/kg) and meloxicam (10 mg & 20 mg/kg) on the melittin-induced nociceptions. Intraplantar injection of melittin caused marked reduction of mechanical threshold that was dose-dependently attenuated by non-selective COX inhibitor (diclofenac) and selective COX-1 inhibitor (piroxicam), but not by COX-2 inhibitor (meloxicam). Melittin-induced flinchings were strongly suppressed by non-selective COX and COX-1 inhibitor, but not by COX-2 inhibitor. None of the COX inhibitors had inhibitory effects on melittin-induced increase of paw thickness (edema). These experimental findings suggest that COX-1 plays an important role in the melittin-induced nociceptive responses.

Change of decreasing blood pressure on pain threshold of spontaneously hypertensive rats / 中国临床药理学与治疗学

AIM: To study the effect of decreasing blood pressure on mechanical and heat pain sensitivity in spontaneously hypertensive rats.METHODS: 15 SHRs were intramuscularly given reserpine(1(?g?kg~(-1)?d~(-1))) on day 4-11.Blood pressure,paw withdrawal mechanical threshold(PWMT) and paw withdrawal thermal latency(PWTL) were measured every day.RESULTS: After the therapy of reserpine in spontaneously hypertensive rats,blood pressure decreased by 50 mmHg,mechanical and heat pain threshold were both decreased(P