Chondroitin sulfate attenuates acid-induced augmentation of the mechanical response in rat thin-fiber muscle afferents in vitro

Abstract

Exercise-induced tissue acidosis augments the exercise pressor reflex (EPR). One reason for this may be acid-induced mechanical sensitization in thin-fiber muscle afferents, which is presumably related to EPR. Acid-induced sensitization to mechanical stimulation has been reported to be attenuated in cultured primary-sensory neurons by exogenous chondroitin sulfate (CS) and chondroitinase ABC, suggesting that the extracellular matrix CS proteoglycan is involved in this sensitization. The purpose of this study was to clarify whether acid-induced sensitization of the mechanical response in the thin-fiber muscle afferents is also suppressed by exogenous CS and chondroitinase ABC using a single-fiber recording technique. A total of 88 thin fibers (conduction velocity <15.0 m/s) dissected from 86 male Sprague-Dawley rats were identified. A buffer solution at pH 6.2 lowered their mechanical threshold and increased their response magnitude. Five minutes after CS (0.3 and 0.03%) injection near the receptive field, these acid-induced changes were significantly reduced. No significant difference in attenuation was detected between the two CS concentrations. Chondroitinase ABC also significantly attenuated this sensitization. The control solution (0% CS) did not significantly alter the mechanical sensitization. Furthermore, no significant differences were detected in this sensitization and CS-based suppression between fibers with and without acid-sensitive channels [transient receptor potential vanilloid 1 (TRPV1), acid-sensing ion channel (ASIC)]. In addition, this mechanical sensitization was not changed by TRPV1 and ASIC antagonists, suggesting that these ion channels are not involved in the acid-induced mechanical sensitization of muscle thin-fiber afferents. In conclusion, CS administration has a potential to attenuate the acidosis-induced exaggeration of muscle mechanoreflex. NEW & NOTEWORTHY We found that exogenous chondroitin sulfate attenuated acid-induced mechanical sensitization in thin-fiber muscle afferents that play a crucial role in the exercise pressor reflex. This finding suggests that extracellular matrix chondroitin sulfate proteoglycans may be involved in the mechanism of acid-induced mechanical sensitization and that daily intake of chondroitin sulfate may potentially attenuate this amplification of muscle mechanoreflex and therefore reduce muscle pain related to acidic muscle conditions.

Insulin potentiates the response to mechanical stimuli in small dorsal root ganglion neurons and thin fibre muscle afferents in vitro

“…Consistent with previous studies (Matsuda et al 2015;Hotta et al 2019), we confirmed that I.M. administration of the control solution did not affect mechanical responsiveness.…”

“…Although group IV afferent fibres are generally more metabolically-sensitive and group III fibres more mechanically-sensitive Jankowski et al 2013), group IV fibres are polymodal in nature with many similarly responding to mechanical stimuli (Kumazawa & Mizumura, 1977). Moreover, group IV fibres are plentiful and more easily identified in the preparation utilized (Taguchi et al 2005;Hotta et al 2015Hotta et al , 2019Matsuda et al 2015). These two characteristics form the rationale for assessing group IV muscle afferent responsiveness in the present study.…”

“…These recordings were made using the methodology that has been reported previously (Hotta et al . , ). We placed an isolated extensor digitorum longus (EDL) muscle with the common peroneal nerve in a test chamber of an organ bath.…”

“…Once a single group IV afferent fibre was identified, we applied a mechanical stimulus (linearly increasing from 0 to 196 mN in 10 s) perpendicularly to the receptive field utilizing a servo‐controlled mechanical stimulator equipped with a 2.3 mm 2 round‐tipped probe (Hotta et al . , ).…”

“…The methods for making the preparations and solutions, applying mechanical stimuli, and recording whole cell and single nerve fibre responses have been reported previously (Kubo et al 2012;Hotta et al 2015Hotta et al , 2019.…”