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

作者：Murase S; Kato K; Taguchi T; Mizumura K^*

来源：European Journal of Pain, 2014, 18(5): 629-638.

DOI：10.1002/j.1532-2149.2013.00411.x

Background
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.
Methods
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 A delta-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.
Results
Mechanical hyperalgesia was observed from 1 h to 1 day after GDNF (0.03 mu M, 20 mu L) injection. The decreased withdrawal threshold was temporarily reversed after intramuscular injection of amiloride (50 mM, 20 mu L), but not capsazepine (50 mu M, 20 mu L). 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 A delta-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.
Conclusions
These results suggest that GDNF increased the response of muscular A delta-fibre afferents to mechanical stimuli, resulting in muscular mechanical hyperalgesia.

• 出版日期2014-5