Inhibitory effects of morphine on evoked responses of ventral posterolateral neurones in spinal nerve ligated rats Abdul Aziz C.B., Chapman V. & Mason R. School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH.	Print Abstract Search PubMed for: Abdul-Aziz CB Chapman V Mason R

The spinothalamic tract, a major pain pathway, terminates at various nuclei in the thalamus, including the ventral posterolateral (VPL) nucleus (Dostrovsky, 2000). Systemic administration of morphine inhibits nociceptive activity of VPL neurons in normal rats (Martin et al., 1996). The aim of this study was to investigate the effect of systemic morphine on the mechanical and thermal-evoked responses of VPL neurons in a rat model of neuropathic pain.

Ligation of spinal nerves (L5/6) or sham surgery, was carried out in isoflurane anaesthetised rats. Two weeks after surgery, in vivo electrophysiological studies were carried out on sham-operated and spinal nerve ligated (SNL) anaesthetised rats (220-300g weight). Extracellular recordings were made with eight-channel microwire electrode arrays (NB Labs, Texas USA) connected to a Plexon Multichannel Acquisition Processor system. Spontaneous and evoked neuronal responses to a range of calibrated monofilaments (7g [innocuous], 20g and 40g [noxious]) and a noxious thermal stimulus (45°C) were measured. Spontaneous activity was subtracted from evoked response. The effects of cumulative doses of intravenous morphine (0.5mg.kg^-1 to 2mg.kg^-1) and naloxone (0.2mg.kg^-1) administered following morphine were studied. Recording sites in the thalamus were determined histologically. Data were analysed using NeuroExplorer (Plexon Inc., Texas USA) and Prism v 3.03. Data are presented as mean maximal % inhibition ± s.e.m. Drug effects were compared to pre-drug control values using Student's t test.

Spontaneous activity of VPL neurons was 5.6 ± 1.3 Hz and 11.0 ± 2.8 Hz for sham and SNL rats respectively (P<0.05). Spontaneous activity of the VPL neurons was not altered by morphine or naloxone in the two groups of rats. Mechanical (7g, 20g and 40g) and thermal-evoked responses of VPL neurons were 3.5 ± 0.5 Hz, 10 ± 2 Hz, 14 ± 2 Hz and 17 ± 1 Hz for sham and 8 ± 1 Hz, 12 ± 1 Hz, 15 ± 1 Hz; 19 ± 2 Hz for SNL rats respectively. There was a significant difference in the 7g-evoked response of VPL neurons of sham and SNL rats (P<0.01).Morphine significantly inhibited 7g-evoked responses in SNL rats (P<0.01), but not sham rats. Morphine inhibited noxious (20g, 40g and 45ºC) evoked responses in sham operated rats and SNL rats (P<0.05 for all). Inhibitory effects of morphine on noxious-evoked responses of VPL neurons in SNL rats were significantly reversed by a lower dose of naloxone (0.2mg.kg^-1;
P< 0.05), than in sham rats (0.4 mg.kg^-1 to1mg.kg^-1; P<0.05).

Here we report a significant increase in innocuous mechanically-evoked responses of VPL neurons in SNL rats, compared to sham controls. Morphine significantly inhibited both innocuous and noxious evoked responses of VPL neurons in SNL rats but only inhibited noxious evoked responses in sham rats. These data suggest that following peripheral nerve injury, there are changes in the opioid receptor system and its control of mechanically-evoked responses of VPL neurones.

CBAA is supported by Universiti Sains Malaysia.

Dostrovsky, J.O. (2000) Prog. Br. Res. 129, 245-257.
Martin, W.J. et. al. (1996) J. Neurosci. 16, 6601-6611.