Effect of continuous activation of spinal metabotropic glutamate receptor 4 on hyperalgesia in a rat model of neuropathic pain: relationship with Gαi

Rui CHEN; Wei JIANG; Hua WANG

ABSTRACT

Objective:

To evaluate the effect of continuous activation of spinal metabotropic glutamate receptor 4 (mGluR4) on hyperalgesia in a rat model of neuropathic pain (NP) and the relationship with inhibitory G protein α (Gαi).

Methods:

Clean-grade healthy adult male Sprague-Dawley rats, weighing 200-250 g, were used in this study.Forty-one rats in which intrathecal catheters were successfully inserted were selected and divided into 4 groups using a random number table

method:

sham operation group (Sham group, n=8), sham operation plus mGluR4 positive allosteric modulator VU0155041 group (Sham+ V group, n=8), NP group ( n=8), and NP plus VU0155041 group (NP+ V group, n=17). The model of NP was established by spinal nerve ligation (SNL) in anesthetized rats.On day 7 after SNL, VU0155041 500 nmol (10 μl) was intrathecally injected, twice a day, for 7 consecutive days in Sham+ V and NP+ V groups, whereas normal saline was used as vehicle control in Sham and NP groups.The 50% paw withdrawal threshold (PWT) was measured before SNL, on day 7 after SNL, at 30 min before and after each intrathecal injection, and at 24 h after the last intrathecal injection.The expression of mGluR4, Gαi1, Gαi2 and Gαi3 in the spinal cord was detected by Western blot before SNL group and on day 7 after SNL and at 24 h after the last intrathecal injection in NP+ V group.

Results:

Compared with Sham group, the PWT was significantly decreased on day 7 after SNL and at 24 h after last intrathecal injection in NP group and NP+ V group ( P<0.05). Compared with NP group, the PWT was significantly increased at 24 h after last intrathecal injection in NP+ V group ( P<0.05). Compared with that on day 7 after SNL, the PWT was significantly increased at 24 h after the last intrathecal injection in NP+ V group ( P<0.05), and no significant change was found in NP group ( P>0.05). The PWT was significantly increased after each intrathecal administration as compared with that before administration in NP+ V group ( P<0.01). The expression of mGluR4 and Gαi3 in the spinal cord was significantly up-regulated on day 7 after SNL compared with that before SNL in NP + V group ( P<0.05), and was increased at 24 h after the last intrathecal injection compared with that on day 7 after SNL ( P<0.05).

Conclusion:

Continuous activation of spinal mGluR4 can reduce the hyperalgesia in a rat model of NP, and the mechanism may be related to Gαi3.