The possibility that pain perception and processing in the CNS results in cellular stress and may influence
heat shock protein (HSP) expression was examined in a rat model of
morphine dependence and withdrawal. Since activation of
pain pathways result in exhaustion of
growth factors, we examined the influence of
cerebrolysin, a mixture of potent
growth factors (
BDNF,
GDNF,
NGF,
CNTF etc,) on
morphine induced HSP expression. Rats were administered
morphine (10 mg/kg, s.c. /day) for 12 days and the spontaneous
withdrawal symptoms were developed by cessation of the drug administration on day 13(th) that were prominent on day 14(th) and continued up to day 15(th) (24 to 72 h periods). In a separate group of rats,
cerebrolysin was infused intravenously (5 ml/kg) once daily from day one until day 15(th). In these animals,
morphine dependence and withdrawal along with HSP immunoreactivity was examined using standard protocol. In untreated group mild HSP immunoreaction was observed during
morphine tolerance, whereas massive upregulation of HSP was seen in CNS during withdrawal phase that correlated well with the
withdrawal symptoms and neuronal damage. Pretreatment with
cerebrolysin did not affect
morphine tolerance but reduced the HSP expression during this phase. Furthermore,
cerebrolysin reduced the
withdrawal symptoms on day 14(th) to 15(th). Taken together these observations suggest that cellular stress plays an important role in
morphine induced
pain pathology and exogenous supplement of
growth factors, i.e.
cerebrolysin attenuates HSP expression in the CNS and induce neuroprotection. This indicates a new therapeutic role of
cerebrolysin in the pathophysiology of drugs of abuse, not reported earlier.