Lesion and electrical stimulation of the ventral tegmental area modify persistent nociceptive behavior in the rat

Abstract

The ventral tegmental area (VTA) has been traditionally related with the control of motor responses. However, some studies show that this area is also involved in the processing of nociceptive information. It has been reported that this nucleus participates in the dissociative analgesia phenomenon. In the few works where electrical stimulation and lesion of the VTA have been performed, evaluated with persistent or chronic pain related behaviors, contradictory results have been obtained. Thus, a more detailed analysis of the role of the VTA in persistent pain is needed. Two series of experiments were performed: lesions of this nucleus were done with radiofrequency, (bilaterally at two points per side using a temperature range from 50 to 80°C), and the VTA was electrically stimulated (10 min daily over 5 days, 2 ms rectangular pulses at 100 Hz during 1 s every 5 s) using two different schemes:10 min before the induction of the nociceptive stimulus and 90 min after the induction of the nociceptive stimulus. The latter allowed us to distinguish if the VTA electrical stimulation had a distinctive antinociceptive effect when applied before or after the induction of the nociceptive stimulus on a persistent pain related behavioral response in the rat, the self injury behavior (SIB). Our results showed that VTA lesions enhanced the occurrence of SIB; while activation of this same nucleus by electrical stimulation after the nociceptive stimulus, but not before, facilitates the analgesic process, expressed as a 1 day delay in SIB onset. These results indicate that the VTA is a brain structure that plays a key role in the processing and modulation of persistent pain information. Data are discussed in terms of the relationship of the VTA with the affective component of pain.