Altier, Nadège (1997) An analysis of the role of midbrain dopamine systems in the suppression of tonic pain. PhD thesis, Concordia University.
It has been considered for some time that the activation of the midbrain ascending dopamine (DA) systems plays a role in the suppression of tonic or persistent pain. For instance, earlier work has shown that substance P (SP), a tachykinin neuropeptide released during pain and stress, acting in the midbrain induces analgesia in the formalin test for tonic pain. The present thesis explored in more depth the role of SP-DA interactions in the suppression of tonic pain, and examined whether the activation of midbrain DA neurons by endogeneous SP might be a mechanism underlying stress-induced analgesia. A first series of experiments were designed to examine the effects of agonists with different affinities for tachykinin NK-1 and NK-3 receptors in the formalin test for tonic pain and, for comparison, the tail-flick test for phasic pain, following infusions into either the ventral tegmental area (VTA) in the midbrain or nucleus accumbens (NAS) in the forebrain. Infusions into either the VTA or NAS of the NK-1 agonist, GR-73632, and the NK-3 agonist, senktide, induced analgesia in the formalin, but not the tail-flick test, suggesting that NK-1 and NK-3 receptors in the VTA and NAS are involved in mediating the inhibition of tonic pain. Pretreatment with the opioid receptor antagonist, naltrexone, did not attenuate the analgesic effects in the formalin test of intra-VTA or intra-NAS infusions of the SP analog, DiMe-C7, GR-73632, or senktide, suggesting that these effects are mediated independently from opioid mechanisms. The idea that exposure to stress inhibits tonic pain by causing, in part, the release of SP in the VTA was supported by the finding that intra-VTA pretreatment with the NK-1 selective receptor antagonist, RP 67580, blocks stress-induced analgesia in the formalin test. Another series of studies were designed to explore the possibility that enhanced DA transmission in the NAS mediates the inhibition of tonic pain. It was found in these studies that intra-NAS pretreatment with DA receptor antagonists attenuates analgesia induced by intra-VTA DiMe-C7, intra-VTA morphine, and intra-NAS amphetamine in the formalin test. It was also found that reduced DA release in midbrain ascending systems, induced by a low autoreceptor-specific dose of apomorphine, prevents the analgesic effect of intra-VTA morphine. The findings revealed throughout the present thesis suggest that part of a pain-suppression system that serves to inhibit tonic pain depends, at least in part, upon the activation of the DA neurons innervating the NAS, and that this pain-suppression system is naturally triggered by exposure to stress and/or pain, through the release of opioids and SP.
|Divisions:||Concordia University > Faculty of Arts and Science > Psychology|
|Item Type:||Thesis (PhD)|
|Pagination:||xiii, 205 leaves : ill. ; 29 cm.|
|Degree Name:||Theses (Ph.D.)|
|Thesis Supervisor(s):||Stewart, Jane|
|Deposited By:||Concordia University Libraries|
|Deposited On:||27 Aug 2009 13:10|
|Last Modified:||08 Dec 2010 10:13|
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