In the present series of studies, contributions of descending pain facilitatory and inhibitory pathways to behavioral pain responses were assessed under physiological conditions in humans and rats, under a simulated weightlessness condition in rats, and in an experimental model of Parkinson’s disease (PD) in rats. A long-term activation of descending pain modulatory pathways was induced by noxious conditioning stimulation to allow determining whether the studied experimental procedures cause decreases or increases in the activity of descending pathways. Acute muscle nociception was induced by intramuscular injection of 5.8% hypertonic saline. Secondary mechanical hyperalgesia was used as an index of the magnitude of descending facilitation, and secondary heat hypoalgesia as an index of the magnitude of descending inhibition. To explore whether heating-needle stimulation (H.N.S.) can promote analgesia due to modulation of descending pain controls, the effect of H.N.S. on descending facilitation and inhibition was also determined in different experimental conditions of the present study. To study whether thalamic dopamine is involved in descending modulation of pain, the effects induced by microinjections of dopamine or dopamine D2 receptor antagonist into the thalamic mediodorsal (MD) / ventromedial (VM) nuclei on descending pain modulation were evaluated. Furthermore, expression of Fos, a marker of neuronal activation, was determined in the spinal cord dorsal horn to reveal a spinal neuronal correlate for descending pain modulation. In the current series of studies, simulated weightlessness and a partial depletion of dopamine in the striatum enhanced endogenous descending facilitation and depressed descending inhibition. In the spinal dorsal horn, changes in Fos expression in the superficial layers were associated with changes in descending facilitation and those in the middle/deep layers with changes in descending inhibition. Intramuscular (i.m.) H.N.S. at an innocuous temperature of 43 C triggered descending inhibition without concomitant activation of descending facilitation both in physiological conditions and in experimental model of PD. In the PD model, dopamine D2 receptors in the thalamic VM nucleus were involved in mediating the enhancement of descending pain inhibition induced by H.N.S. applied at the temperature of 43 C. In humans, i.m. H.N.S. applied at the non-painful temperature of 43 C enhanced selectively descending inhibition, and it may be explained by a difference in the density of capsaicin- and heat-sensitive fibers innervating these heating-needle stimulation targets. Injection of capsaicin that selectively activates C-fibers produced stronger pain in acupoints than in non-acupoints.
|Tila||Julkaistu - 2020|
|OKM-julkaisutyyppi||G5 Tohtorinväitöskirja (artikkeli)|
- 3111 Biolääketieteet
- 1184 Genetiikka, kehitysbiologia, fysiologia