Histomorphological Effects of Repeated Administration of the TRPA1 Antagonist HC-030031 on Intrafusal and Extrafusal Muscle Fibers in Healthy Young Rats

Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel expressed in primary sensory neurons and has been proposed as a therapeutic target for pain management. However, the effects of repeated administration of a TRPA1 antagonist on peripheral tissue morphology remain unclear. This study examined whether repeated HC-030031 administration affected the histomorphology of skeletal muscle fibers and muscle spindles in rats. Male Fischer 344 rats were assigned to a control group (Con, n = 10, 12.6 ± 3.3 weeks) or an HC-030031-treated group (HC, n = 10, 13.2 ± 3.7 weeks). HC-030031 was administered subcutaneously once weekly for four weeks. Tibialis anterior muscles were harvested and analyzed using histochemical and morphometric methods. Morphometric analyses included muscle mass, myofiber cross-sectional area (FCSA), roundness of extrafusal muscle fibers, NADH-TR staining intensity-based assessment, and structural parameters of muscle spindles and intrafusal fibers. No significant differences were observed between the groups in body weight, muscle mass, extrafusal FCSA, or fiber roundness. NADH-TR staining was used to distinguish fibers with darker or lighter staining intensity, and FCSA was compared between the Con and HC groups within each staining-based fiber subset. No group differences were detected in the FCSA of either subset. Similarly, no significant differences were observed in intrafusal FCSA, intrafusal fiber roundness, the number of intrafusal fibers per muscle spindle, or muscle spindle density. These findings indicate that repeated HC-030031 administration was not associated with detectable histomorphological alterations in skeletal muscle fibers or muscle spindles under resting conditions in young adult male rats.