Neonatal capsaicin treatment in rats induces chronic hyperthermia resulting in infectious disease

Abstract

Treatment of neonatal animals with capsaicin has previously been associated with long-lasting hyperthermia and severe cutaneous lesions. The present study analyzed the effects of capsaicin-induced hyperthermia on the occurrence of infectious disease and pruritic dermatitis in a rat model. Pregnant Sprague-Dawley (SD) rats were obtained 1 week prior to parturition. Pups from each litter were randomly assigned to the following experimental groups: Capsaicin-treated (cap-treated; n=10) or vehicle-treated (n=5). Capsaicin (50 mg/kg) or vehicle were systemically administered to the SD rat pups (age, 48 h), after which body temperature was measured using a biotelemetry system, and the effects of hyperthermia on the ability of the rat pups to resist bacterial infection were analyzed. Furthermore, pruritus-induced scratching behavior and dermatitis were assessed, and changes in interleukin (IL)-4- and IL-13-induced immunoglobulin E expression were measured. Treatment of neonatal rats with capsaicin resulted in chronic hyperthermia, which had negative effects on the host immune defense response. The expression levels of T-helper type 2 cell-associated cytokines were significantly increased (P<0.01) in the cap-treated rats following bacterial infection with or. Furthermore, cap-treated rats exhibited pruritus-induced scratching behavior and dermatitis. The results of the present study suggested that treatment of neonatal rats with capsaicin induces chronic hyperthermia and decreases the effectiveness of the host defense system. Therefore, a cap-treated neonatal rat model may be considered useful when investigating the association between hyperthermia and infectious disease.

Changes in TRPV1-Mediated Physiological Function in Rats Systemically Treated With Capsaicin on the Neonate

“…The difference between TRPV1 antagonist and neonatal capsaicin treatment is that the hyperthermic effect of capsaicin treatment in neonates is long-lasting [10]. Previous studies on body temperature changes following topical or neonatal capsaicin treatment are listed in Table 3 [13,[38][39][40][41]. Numerous studies have been carried out on the analysis of the effect of hyperthermia on immune cell subsets targeting the tumor, and upregulation of interleukin induced T lymphocyte proliferation by TRPV-1 activation was found to be increased by hyperthermia [42].…”

“…Activation of TRPV1 expressed in sensory neurons leads to inflammatory diseases, such as bronchoconstriction, tracheal mucosal edema, and inflammatory cell chemotaxis [45]. A related study on neonatal capsaicin treatment indicated that induction of constant and permanent hyperthermia in the body might induce an abnormal physiological function related to the body defence system [13]. Brown adipose tissue present in human and animal newborns is responsible for maintaining body temperature and is essential for thermogenesis.…”

“…Brown adipose tissue is rapidly lost postnatally, and this process gets concluded within the first few years of life. However, the volume of brown adipose tissue increased more as neonatal capsaicin-treated rats grew into adults [13]. Although the mechanism has not been clarified yet, it is anticipated that the abnormal phenotype is mediated by the downregulation of TRPV1 followed by the overload of thermoregulation activity in brown adipose tissues [13].…”

“…However, the volume of brown adipose tissue increased more as neonatal capsaicin-treated rats grew into adults [13]. Although the mechanism has not been clarified yet, it is anticipated that the abnormal phenotype is mediated by the downregulation of TRPV1 followed by the overload of thermoregulation activity in brown adipose tissues [13]. Leptin contributes to cutaneous antimicrobial defense system by upregulating the expression of defensins [48].…”

“…As the mechanism of function mediated by TRPV1 in the regulation of body temperature has been newly established, there is an opportunity to broaden the field of observation toward physiological changes [9]. In the process of conducting various neurophysiological studies on TRPV1 by administering capsaicin immediately after birth to neonates, various interesting changes in the physiological functions have been reported [10][11][12][13][14][15][16][17][18]. Accordingly, the unique physiological changes that may occur due to exposure to capsaicin to neonates are reviewed herein.…”