Augmented Mechanical Response of Muscle Thin-Fiber Sensory Receptors Recorded from Rat Muscle–Nerve Preparations In Vitro After Eccentric Contraction

Abstract

Taguchi, Toru, Jun Sato, and Kazue Mizumura. Augmented mechanical response of muscle thin-fiber sensory receptors recorded from rat muscle-nerve preparations in vitro after eccentric contraction. J Neurophysiol 94: 2822Neurophysiol 94: -2831Neurophysiol 94: , 2005 doi:10.1152/jn.00470.2005. Unaccustomed strenuous exercise, especially that from eccentric muscular work, often causes muscle tenderness, which is a kind of mechanical hyperalgesia. We developed an animal model of delayed-onset muscle soreness (DOMS) from eccentric muscular contraction (ECC) in rats and demonstrated the existence of muscle tenderness by means of behavioral pain tests and c-Fos protein expression in the spinal dorsal horn. The purpose of the present study was to examine whether the sensitivities of muscle thin-fiber sensory receptors to mechanical, chemical, and thermal stimuli were altered after repetitive ECC in a rat model of DOMS. ECC was caused in the animals by electrical stimulation of the common peroneal nerve innervating the extensor digitorum longus muscle (EDL) while the muscle was being stretched. Activities of single thin-fiber receptors (sensitive to pressure but insensitive to stretch, with conduction velocity slower than 2.0 m/s) were recorded from muscle (EDL)-nerve preparations in vitro 2 days after ECC when mechanical hyperalgesia was at its peak. The mechanical threshold of thin-fiber receptors was found to be very much lower in the ECC preparations than in the nontreated control (CTR) [median 65.4 mN (interquartile range [IQR]; 46.6 -122.0 mN) in the CTR preparation vs. 38.2 mN (IQR; 26.8 -55.8 mN) in the ECC, P Ͻ 0.001]. In addition, the total number of evoked discharges during a ramp mechanical stimulus, taken as an index of the magnitude of the mechanical response, nearly doubled in the ECC preparations compared with the CTR [24.7 spikes (IQR; 14.2-37.1 spikes) in the CTR preparation vs. 54.2 spikes (IQR; 24.3-89.0 spikes) in the ECC, P Ͻ 0.001]. In contrast, the numbers of discharges induced by chemical (pH 5.5, lactic acid, adenosine triphosphate, and bradykinin) and thermal (cold and heat) stimuli were not different between the two preparations. These results suggest that augmentation of the mechanical response in muscle thin-fiber sensory receptors might be related to the muscle tenderness in DOMS after ECC.

Bradykinin and Nerve Growth Factor Play Pivotal Roles in Muscular Mechanical Hyperalgesia after Exercise (Delayed-Onset Muscle Soreness)

“…However, since bradykinin, kallidin, and kallidin-like peptide bind B 2 bradykinin receptors, and B 2 antagonist cannot differentially block the action of these three, here we used "bradykinin" to refer to all three of these kinins. The absence of an effect from bradykinin receptor antagonists administered after development of DOMS showed that bradykinin is not the substance that maintains mechanical hyperalgesia, which means that bradykinin is not responsible for the increased mechanical sensitivity of thin-fiber receptors after LC (Taguchi et al, 2005b).…”

“…In the present experiment, we examined involvement of bradykinin and NGF in DOMS using a rat model of DOMS in which we previously showed the existence of mechanical hyperalgesia (Taguchi et al, 2005a) and increased mechanical sensitivity of muscle thin-fiber afferents (Taguchi et al, 2005b). We found that bradykinin triggers development of muscular mechanical hyperalgesia and NGF serves in its maintenance by sensitizing muscle C-fiber receptors to mechanical stimulation.…”

“…The methods of obtaining single-fiber activities, stimulation, and analysis were described previously (Taguchi et al, 2005b). Briefly, the EDL muscle from both hindlimbs was carefully removed with the common peroneal nerve attached under pentobarbital anesthesia (50 mg/kg, i.p.).…”

“…To investigate this possibility, we recorded single-muscle, thin-fiber activities from the EDL muscle-common peroneal nerve preparations in vitro (Taguchi et al, 2005b) and examined whether NGF sensitized the mechanical sensitivity in the periphery of these preparations in a short period.…”

Mechanism and implications of hyperpnea exaggeration at the onset of exercise in mechanical hyperalgesia after eccentric exercise

“…2, 4-2). Previous animal experiments have revealed that the threshold of response of thin muscle afferents to mechanical stimuli was reduced in muscle with DOMS after ECC 49) . The exact mechanism responsible for the sensitization of thin muscle afferents to mechanical stimuli in muscles with DOMS has not yet been clarified.…”