Pretreatment with opioids enhances afferent induced long-term potentiation in the rat dorsal horn
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Eileen Hauge Kjellsen
Objectives
Opioids are increasingly used against chronic nonmalignant pain. Long-term opioid treatment may be associated with the development of hyperalgesia. Long term facilitation (LTF) of C-fibre evoked firing of wide dynamic range neurons in the spinal dorsal horn in response to conditioning stimulation (CS) of afferent fibres is a widely studied cellular model of spinal nociceptive sensitization. In a rat model with recording of single neurone responses we have previously demonstrated that seven days of opioid pretreatment enhances the stimulus-evoked LTF (Fig. 1, Haugan 2008 [1]). In this study we looked at the effect of long-term pretreatment with morphine on longterm potentiation (LTP) of C-fibre evoked dorsal horn field potentials, a widely used model of spinal hyperexcitability.
Methods
Female rats (Sprague-Dawley, n = 16) were implanted with subcutaneous Alzet mini-osmotic pumps during short-lasting Isoflurane anaesthesia. The rats were randomised to either s.c. infusion of morphine (20 mg/kg/d) or saline (NaCl 9 mg/ml) and blinded to the experimenter. After 7 days the rats were anaesthetised with intraperitoneal urethane (1.4–1.65 g/kg). C-fibre evoked field potentials in the spinal cord dorsal horn were recorded at the level of segments L4-L5. Both the potentiating stimulation (100 Hz, 4 trains, each train 2 s duration, 10 s intervals) and the test stimulation (single stimuli) were given to the sciatic nerve at C-fibre strength.
Extracellular single unit recordings. From Haugan (2008).
Field potentials after conditioning stimulation after treatment with morphine or saline.
Results
There was a tendency that seven days of morphine pretreatment increased the potentiation of C-fiber evoked field potentials by conditioning stimulation compared to the saline group (Fig. 2).
Conclusion
Our results support our previous findings and indicate that animals treated with long term opioid show amplification of stimulus-induced central sensitisation compared to opioid naïve animals.
References
[1] Haugan F, Rygh LJ, Tjølsen A. Ketamine blocks enhancement of spinal long-term potentiation in chronic opioid treated rats. Acta Anaesthesiol Scand 2008;52:681-7.Search in Google Scholar
© 2010 Scandinavian Association for the Study of Pain
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