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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\u2009+\u2009Radiation), groups IV (Reserpine\u2009+\u2009Naloxone\u2009+\u2009Radiation), and group V (Reserpine\u2009+\u2009Diclofenac). Pain assessment by tail-flick test and Haffner\u2019s tail clip method were performed, in addition to estimation of serum substance-P (SP) and tumor necrosis factor-\u03b1 (TNF-\u03b1) 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\u2019s 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\u2019s clip test was significantly blocked upon the administration of naloxone prior to irradiation as compared to the reserpine\u2009+\u2009radiation group. Also, this study showed that the reserpine intoxication induced an elevation in rat brain MDA and NO, and serum TNF-\u03b1 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.<\/jats:p>","DOI":"10.1038\/s41598-026-44637-8","type":"journal-article","created":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T07:55:10Z","timestamp":1775894110000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Central and peripheral analgesia in irradiated rats: reserpine-induced pain model"],"prefix":"10.1038","volume":"16","author":[{"given":"Mostafa","family":"Saif-Elnasr","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,11]]},"reference":[{"key":"44637_CR1","unstructured":"Loeser, J. D., Butler, S. H., Chapman, C. R. & Turk, K. C. 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