Frequency components of systolic blood pressure variability reflect vasomotor and cardiac sympathetic functions in conscious rats.

In this study, after confirming the suppression of autonomic nervous function by isoflurane anesthesia using autonomic antagonists, we pharmacologically investigated the involvement of vasomotor and cardiac sympathetic functions in systolic blood pressure variability (SBPV) frequency components in conscious rats at rest and during exposure to low-ambient temperature (LT-exposure, 9°C for 90 min). Under unanesthesia, phentolamine administration (α-adrenoceptor antagonist, 10 mg/kg) decreased the mid-frequency component (MF 0.33-0.73 Hz) and inversely increased the high-frequency component (HF 1.3-2.5 Hz). The increased HF was suppressed by subsequent treatment with atenolol (ß-adrenoceptor antagonist, 10 mg/kg), but not with atropine (muscarinic receptor antagonist, 10 mg/kg). Moreover, phentolamine administration after atenolol decreased MF, but did not increase HF. LT-exposure increased MF and HF; however, phentolamine pretreatment suppressed the increased MF during LT-exposure, and atenolol pretreatment dose-dependently decreased the increased HF. These results suggest that MF and HF of SBPV may reflect α-adrenoceptor-mediated vasomotor function and ß-adrenoceptor-mediated cardiac sympathetic function, respectively, in the conscious state.

Low rather than high dose lipopolysaccharide 'priming' of muscle provides an animal model of persistent elevated mechanical sensitivity for the study of chronic pain.

Experimental animal pain models involving peripheral nerve lesions have expanded the understanding of the pathological changes caused by nerve damage. However models for the pathogenesis of chronic pain patients lacking obvious nerve injuries have not been developed to the same extent. Guided by clinical observations, we focused on the initiating noxious event, the context when applying nociceptive stimulation targeting long-lasting pain elicited by muscle insult. The administration of a nociceptive agent (6% hypertonic saline: HS; 5-time repeated-injection: HS5) after pretreatment with an immuno-inflammatory agent (lipopolysaccharide: LPS, 2 µg/kg) into one gastrocnemius muscle produced markedly long-persisting biphasic sustained mechanical hypersensitivity on the plantar surface of both hindpaws. In the acute phase, the blockade of afferent inputs from the injected-site was effective in returning the contralateral enhanced-responses to baseline levels. In contrast, similar blockade during the chronic phase did not affect the contralateral enhanced-responses, indicating that the hypersensitivity in the two phases was probably induced by different mechanisms. However, increasing the dose of LPS (20 µg/kg) before applying HS5 eliminated the development of mechanical hypersensitivity in the chronic phase, while the hypersensitivity in the acute phase was significantly more severe than with low-dose LPS-pretreatment. In this model, the development of hypersensitivity could be modulated by manipulating LPS-doses prior to noxious stimulation. This novel chronic pain model based on a preceding 'priming' myalgic stimulus provides an intriguing means for studying the pathogenesis of chronic pain.