pattismith
Senior Member
- Messages
- 3,941
Thin‐fibre receptors expressing acid‐sensing ion channel 3 contribute to muscular mechanical hypersensitivity after exercise
Takanori Matsubara
First published: 17 July 2019
Abstract
Background
Delayed onset muscle soreness (DOMS) is characterized by mechanical hyperalgesia after lengthening contractions (LC). It is relatively common and causes disturbance for many people who require continuous exercise, yet its molecular and peripheral neural mechanisms are poorly understood.
Methods
We examined whether muscular myelinated Aδ‐fibres, in addition to unmyelinated C‐fibres, are involved in LC‐induced mechanical hypersensitivity, and whether acid‐sensing ion channel (ASIC)‐3 expressed in thin‐fibre afferents contributes to this type of pain using a rat model of DOMS.
The peripheral contribution of ASIC3 was investigated using single‐fibre electrophysiological recordings in extensor digitorum longus muscle‐peroneal nerve preparations in vitro.
Results
Behavioural tests demonstrated a significant decrease of the muscular mechanical withdrawal threshold following LC to ankle extensor muscles, and it was improved by intramuscular injection of APETx2 (2.2 μM), a selective blocker of ASIC3. The lower concentration of APETx2 (0.22 µM) and its vehicle had no effect on the threshold. Intramuscular injection of APETx2 (2.2 μM) in naïve rats without LC did not affect the withdrawal threshold. In the ankle extensor muscles that underwent LC one day before the electrophysiological recordings, the mechanical response of Aδ‐ and C‐fibres was significantly facilitated (i.e. decreased response threshold and increased magnitude of the response). The facilitated mechanical response of the Aδ‐ and C‐fibres was significantly suppressed by selective blockade of ASIC3 with APETx2, but not by its vehicle.
Conclusions
These results clearly indicate that ASIC3 contributes to the augmented mechanical response of muscle thin‐fibre receptors in delayed onset muscular mechanical hypersensitivity after LC.
Significance
Here, we show that not only C‐ but also Aδ‐fibre nociceptors in the muscle are involved in mechanical hypersensitivity after lengthening contractions, and that acid‐sensing ion channel (ASIC)‐3 expressed in the thin‐fibre nociceptors is responsible for the mechanical hypersensitivity. ASIC3 might be a novel pharmacological target for pain after exercise.
Takanori Matsubara
First published: 17 July 2019
Abstract
Background
Delayed onset muscle soreness (DOMS) is characterized by mechanical hyperalgesia after lengthening contractions (LC). It is relatively common and causes disturbance for many people who require continuous exercise, yet its molecular and peripheral neural mechanisms are poorly understood.
Methods
We examined whether muscular myelinated Aδ‐fibres, in addition to unmyelinated C‐fibres, are involved in LC‐induced mechanical hypersensitivity, and whether acid‐sensing ion channel (ASIC)‐3 expressed in thin‐fibre afferents contributes to this type of pain using a rat model of DOMS.
The peripheral contribution of ASIC3 was investigated using single‐fibre electrophysiological recordings in extensor digitorum longus muscle‐peroneal nerve preparations in vitro.
Results
Behavioural tests demonstrated a significant decrease of the muscular mechanical withdrawal threshold following LC to ankle extensor muscles, and it was improved by intramuscular injection of APETx2 (2.2 μM), a selective blocker of ASIC3. The lower concentration of APETx2 (0.22 µM) and its vehicle had no effect on the threshold. Intramuscular injection of APETx2 (2.2 μM) in naïve rats without LC did not affect the withdrawal threshold. In the ankle extensor muscles that underwent LC one day before the electrophysiological recordings, the mechanical response of Aδ‐ and C‐fibres was significantly facilitated (i.e. decreased response threshold and increased magnitude of the response). The facilitated mechanical response of the Aδ‐ and C‐fibres was significantly suppressed by selective blockade of ASIC3 with APETx2, but not by its vehicle.
Conclusions
These results clearly indicate that ASIC3 contributes to the augmented mechanical response of muscle thin‐fibre receptors in delayed onset muscular mechanical hypersensitivity after LC.
Significance
Here, we show that not only C‐ but also Aδ‐fibre nociceptors in the muscle are involved in mechanical hypersensitivity after lengthening contractions, and that acid‐sensing ion channel (ASIC)‐3 expressed in the thin‐fibre nociceptors is responsible for the mechanical hypersensitivity. ASIC3 might be a novel pharmacological target for pain after exercise.