Resumo

Introduction: Emotional states can significantly modify the nociceptive perception. For instance, anticipatory anxiety is a factor which may lead to pain exacerbation. However, mechanisms underlying this phenomenon remain elusive. The transient receptor potential vanilloid type 1 (TRPV1) channel is a molecular sensor for nociceptive stimuli in primary afferent neurons and its role in emotions are now being elucidated. Objective: The aim of the present study was to investigate whether the infusion of TRPV1 channels agonist capsaicin (CPS) into the dorsolateral periaqueductal gray (dlPAG), at putative anxiogenic-like doses, would intensify the nociception and inflammatory parameters exhibited by rats in the knee-joint incapacitation test. Methods: Male Wistar rats were implanted with guide cannula aimed at the dlPAG. One-week after surgery, in experiment 1, subjects were infused into the dlPAG with vehicle (VEH; phosphate buffered saline containing 15 % of dimethyl sulfoxide) or CPS (0.1-5.0 nmol/0.2 μL), and 10 min later exposed for 5 min to the elevated-plus maze (EPM), an animal test of anxiety. In experiment 2, we verified whether the TRPV1 channel antagonist capsazepine (CPZ), at an uneffective dose, would block the CPS effects. The following groups were carried out: VEH-VEH; VEH-CPS 1.0 nmol; CPZ 0.6 nmol-VEH and CPZ 0.6 nmol-CPS 1.0 nmol. Behavioral measures scored were the percentage of open-arm time (%OAT) and open-arm entries (%OAE), stretched-attend postures (SAPs), and enclosed-arm entries (EAE). To investigate the intra-dlPAG CPS effects on inflammatory nociception, in experiment 3, another group of rats was evaluated during 6 h in the carrageenan/LPS-induced knee-joint incapacitation test. The behavioral measure scored was the paw elevation time (PET) during forced walk and the articular diameter (AD). All results are presented as mean ± S.E.M. Results: ANOVA followed by Duncan´s test showed a reduction (p<0.05) in %OAT [VEH = 18 ± 4, CPS 1.0 nmol = 5 ± 2] and %OAE [VEH = 37 ± 6, CPS 1.0 nmol = 19 ± 4] in rats exposed to the EPM test after CPS infusion into the dlPAG. This anxiogenic-like effect was antagonized by CPZ 0.6 nmol [%OAT: VEH-VEH = 23 ± 5, VEH-CPS = 6 ± 2, CPZ-VEH = 17 ± 3, CPZ-CPS = 17 ± 4; %OAE: VEH-VEH = 43 ± 4, VEH-CPS = 21 ± 4, CPZ-VEH = 35 ± 6, CPZ-CPS = 35 ± 5]. No significant changes were observed for SAPs and EAE. At the dose of 1.0 nmol, CPS also augmented the PET in the arthritic-induced incapacitation test from the second [VEH = 22 ± 7 s, CPS = 38 ± 6 s] to the third hour [VEH = 14 ± 2 s, CPS = 32 ± 7 s] after the LPS injection. A similar effect was found in the AD on the second hour [VEH = 0.05 ± 0.03 mm, CPS 1.0 nmol = 0.11 ± 0.01 mm]. Conclusions: The TRPV1 channel activation in the dlPAG increased inhibitory avoidance behavior, suggesting an anxiogenic-like effect, profile that was blocked when capsazepine was microinjected before capsaicin. At this anxiogenic-like dose, CPS also increased the nociceptive response and articular diameter. The present results support a TRPV1channel role in controlling anxiety-related behavior and substantiate the hypothesis that a mild dlPAG chemical stimulation induced by the activation of TRPV1 channels produces an anticipatory anxiety which may intensify nociception and inflammatory edema. Financial support: CNPq and FAPESC, Brazil.