Central and peripheral analgesia in irradiated rats: reserpine-induced pain model

Abstract Over one-third of the world’s population suffers from persistent or recurrent pain. Thus, this study was designed to investigate the possible analgesic effect offered by a low gamma-irradiation dose, as well as to elucidate its mechanisms of action; either through central, peripheral or indirect analgesia via the attenuation of oxidative stress and/or inflammation that are the proposed components of pain induction in the reserpine-induced model. Thirty male rats were divided into: group I (Normal), group II (Reserpine), group III (Reserpine + Radiation), groups IV (Reserpine + Naloxone + Radiation), and group V (Reserpine + Diclofenac). Pain assessment by tail-flick test and Haffner’s tail clip method were performed, in addition to estimation of serum substance-P (SP) and tumor necrosis factor-α (TNF-α) levels, and brain contents of nitric oxide (NO), malondialdehyde (MDA) and dopamine (DA). Results displayed that administration of reserpine induced a significant reduction in both peripheral and central pain thresholds. However, low dose radiation induced a significant delay in pain latency in both tail-flick and Haffner’s tail clip tests, as compared to reserpine untreated group. Low dose radiation peripheral analgesic effect was similar to the analgesia offered by diclofenac. Low dose irradiation-induced analgesia revealed in Haffner’s clip test was significantly blocked upon the administration of naloxone prior to irradiation as compared to the reserpine + radiation group. Also, this study showed that the reserpine intoxication induced an elevation in rat brain MDA and NO, and serum TNF-α and SP levels, as well as a significant reduction in brain DA content as compared to the normal group. On the other hand, irradiation of reserpinized rats resulted in a restoration of all these parameters. Finally, it could be concluded that low radiation dose exerts analgesic effects through functional modulation of nociceptive pathways, potentially involving opioid-related mechanisms, as well as antioxidant and/or anti-inflammatory effects.