br Introduction Radiotherapy is the most common modality for

Introduction Radiotherapy is the most common modality for treating human cancers. About 80% of the patients need such treatment either for curative or palliative purpose [1]. Radiation exposure may produce many harmful effects on living organisms [2]. Gamma irradiation initiates chemical changes in the cellular components as a result of immediate consequence of the penetration of ionizing radiation through the living systems. The biological effect differs according to irradiation dose [3]. It was observed that renal damage may be produced as evidenced by the reduction of renal function at all doses above 4 Gy [4]. Furthermore, the whole body exposure of rats to γ-radiation at a dose of 3.5 Gy causes an increase in the levels of AST and ALT [5]. Pain is one of the most common associated symptoms of cancer which may be a result of tumors expansion, nerve compression, infiltration by the tumor, or infections in malignant ulcers [6]. Radiation exposure may also lead to pain in which chemical stimuli are released from the damaged purchase SIRT1/2 Inhibitor IV [7]. These stimuli act on the nociceptors resulting in central or peripheral pain. However more than 80% of those patients treated with radiation report an analgesic effect, usually during the first days after treatment, that is sustained for months thereafter [8,9]. Theories, mostly originating from clinical studies, attempting to explain the antinociceptive effect of radiation include a decreased number of carcinomatous cells, an inhibition of osteoclasts, decreases in local algogenic substances, immune response, and neural transmission [10–12]. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most useful medications for peripheral nerve injury as it is accompanied by inflammatory response. This response involves increased production of prostaglandins (PGs) which enhances sodium current and calcium influx in peripheral nociceptive neurons [13] and increased central neurotransmitter release and depolarization of second order nociceptive neurons. NSAIDs inhibit cyclooxygenase COX-1 or COX-2 or both and block the production of prostaglandins [14,15]. Ketorolac is a non-selective COX – inhibitor [16], may be strong enough to be used in treating cancer pain.
Material and Methods
Results
Discussion In the present study we aimed to evaluate the analgesic effect of the NSAID, ketorolac in irradiated animals. Furthermore, investigation of the toxicological effects of ketorolac in irradiated animals was also performed. The formalin test is commonly used to evaluate the analgesic effect of drug. Therefore, the method for testing the anti-nociception was selected so that both centrally and peripherally mediated effects were investigated. In formalin test there are two phases of nociceptive response. The first (0–5 min) is the early phase of C fiber activation (central effect) corresponds to neurogenic pain, and the second (15–30 min) is the late phase (peripheral effect) corresponds to inflammatory pain appeared to be dependent on the combination of an inflammatory reaction in the peripheral tissue and functional changes in the dorsal horn of the spinal cord [18]. In the present study, both irradiation and ketorolac inhibit the nociceptive response of the animals. Irradiation in the early phase induced inhibition recorded after one day of radiation exposure which was more than that reported after 7 days of radiation exposure. However, such effect was much more pronounced in the late phase after 7 days of irradiation rather than after 1 day post radiation exposure. The delayed response in the early phase in the irradiated animals was more significant after 7 days post radiation exposure, suggesting that irradiation may reverses the increased expression of several neurochemical markers of nociception in the cervical spinal cord suggesting that part of the analgesic effect is due to altered nociceptive processing in the central nervous system [21]. Moreover, irradiation may induce alterations in the levels of the neurotransmitters such as serotonin level in the central nervous system.