Effects of neonatal capsaicin treatment on stress induced analgesia and hyperalgesia in Tail-Flick test in male rats

Background & Objective: It is reported that acute forced swimming stress induces analgesia immediately, and chronic stress induces hyperalgesia. Whereas in response to nociceptive stimulation, small-diameter C-fibers of the excitatory system in the dorsal horn of the spinal cord are activated, therefore, in the present study, the effects of C-fiber lesion in stress and dexamethasone-induced analgesia and hyperalgesia in acute and chronic forms were investigated using Tail-Flick test. Methods: Adults Wistar male rats (180-200 g) were assigned into three groups (n=7): C-normal (intact C-fibers), sham (received capsaicin vehicle at neonate stage) and C-lesion (received capsaicin at neonate stage). Forced swim stress (10 min/day) in water (18±1 oC) was considered as acute stress and repeated daily forced swim stress as chronic stress, also single-dose of dexamethasone (2 mg/kg, i.p.) was considered as acute dexamethasone and repeated for three days as chronic dexamethasone. Neonatal capsaicin treatment was used for C-fibers depletion. The nociceptive thermal threshold was assessed using Tail-Flick test. Results: In C-lesion group, thermal pain sensitivity was reduced (P<0.001). Acute stress in C-normal group, reduced pain (P<0.001) and in C-lesion group, it caused deeper antinociception in Tail-Flick (P<0.001). Chronic stress and acute-chronic dexamethasone in C-normal group, created hyperalgesia (P<0.001) and induced analgesia in C-lesion groups (P<0.01). Conclusion: It seems that presence of C-fiber is so important in thermal pain transmission in Tail-Flick test; therefore, C-fiber lesion, reduces pain sensitivity (analgesia), increases antinociception effects of acute stress, decreases hyperalgesia of chronic-stress and acute-chronic dexamethasone. Neurology Asia 2015; 20(1) : 65 – 72 Address correspondence to: Dr. Masoud Fereidoni, Department of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran. P.O. Box: 9177948974; Tel: +98-915-5242015; Fax: +98-511-8762227; Email: [email protected] INTRODUCTION Noxious stimuli are carried in the central nervous system (CNS) by two kinds of fibers; anatomically, there are two broad groups of sensory fibers: myelinated A-fibers and unmyelinated C-fibers with the smaller diameter. Peripheral terminals of Aδ-fibers are mechanical receptors that usually, do not respond to thermal and chemical stimuli whilst C nociceptors respond to mechanical, chemical and thermal stimuli. TRPV-1 is a ligandgated, non-selective cation channel. In addition to being sensitive to capsaicin, TRPV-1 responds to thermal stimuli, protons and its activity might be enhanced within the acidic environment of inflamed tissues. In addition of C-fibres also, there are existed on some Aδ-fibers. Pain due to Aδ-fibers stimulation travels quicker (5-30 meters/ second) than the C-fibers (0.5-2 meters/second). Analgesia or hyperalgesia occurs in animals under different conditions such as stress. An increase in pain threshold following acute exposure to painful or stressful events was demonstrated and introduced as stress–induced analgesia. Although it has been shown that chronic forced swimming stress also induces hyperalgesia. On the other hand, acute administration of dexamethasone (2 mg/kg, i.p.) produces hyperalgesia almost after 30 minutes in mimicry of corticosterone secretion. Nevertheless of the existence of remarkable information on stress-induced hyperalgesia, what remains to be fully elucidated is the involvement of different systems or paths in this circumstances. Therefore, the roles of C-fibers during the effects of stress on pain are questioned in this study. Dexamethasone as a synthetic glucocorticoid can Neurology Asia March 2015 66 help for mimicry of a part of the stress activation effects on pain and is used here for more elucidation of the roles of C-fibers on the pain system while of stress. Whereas importance of C-fibers on stress-induced analgesia/hyperalgesia and dexamethasone-induced hyperalgesia are not elucidated in detail; this research is done to clarify them at least partially.