Glial cell line‐derived neurotrophic factor sensitized the mechanical response of muscular thin‐fibre afferents in rats

Abstract

The role of glial cell line-derived neurotrophic factor (GDNF) in pain and muscular nociceptor activities is not well understood. We examined pain-related behaviour and mechanical response of muscular thin-fibre afferents after intramuscular injection of GDNF in rats. GDNF and antagonist to transient receptor potential V1 or acid-sensing ion channels were injected into rat gastrocnemius muscle and muscular mechanical hyperalgesia was assessed with a Randall-Selitto analgesiometer. Activities of single C- (conduction velocity < 2.0 m/s) and Aδ-fibres (conduction velocity 2.0-12.0 m/s) were recorded from extensor digitorum longus muscle-nerve preparations in vitro. The changes in the responses to mechanical stimuli before and after GDNF injection were recorded. Mechanical hyperalgesia was observed from 1 h to 1 day after GDNF (0.03 μM, 20 μL) injection. The decreased withdrawal threshold was temporarily reversed after intramuscular injection of amiloride (50 mM, 20 μL), but not capsazepine (50 μM, 20 μL). In single-fibre recordings, both phosphate buffered saline (PBS) and GDNF failed to induce any significant discharges. GDNF significantly enhanced the mechanical response when compared with the PBS group, but only in Aδ-fibre afferents. C-fibres were not affected. Significantly lowered threshold and increased response magnitude to mechanical stimuli were observed 30 or 60-120 min after injection. These times are compatible with the timing of the onset of the hyperalgesic effect of GDNF. These results suggest that GDNF increased the response of muscular Aδ-fibre afferents to mechanical stimuli, resulting in muscular mechanical hyperalgesia.