Mechanical stimulation of cervical vertebrae modulates the discharge activity of ventral tegmental area neurons and dopamine release in the nucleus accumbens

Abstract

Background: Growing evidence suggests that mechanical stimulation modulates substrates in the supraspinal central nervous system (CNS) outside the canonical somatosensory circuits. Objective/Methods: We evaluate mechanical stimulation applied to the cervical spine at the C7-T1 level (termed "MStim") on neurons and neurotransmitter release in the mesolimbic dopamine (DA) system, an area implicated in reward and motivation, utilizing electrophysiological, pharmacological, neurochemical and immunohistochemical techniques in Wistar rats. Results: Low frequency (45e80 Hz), but not higher frequency (115 Hz), MStim inhibited the firing rate of ventral tegmental area (VTA) GABA neurons (52.8% baseline; 450 s) while increasing the firing rate of VTA DA neurons (248% baseline; 500 s). Inactivation of the nucleus accumbens (NAc), or systemic or in situ antagonism of delta opioid receptors (DORs), blocked MStim inhibition of VTA GABA neuron firing rate. MStim enhanced both basal (178.4% peak increase at 60 min) and evoked DA release in NAc (135.0% peak increase at 40 min), which was blocked by antagonism of DORs or acetylcholine release in the NAc. MStim enhanced c-FOS expression in the NAc, but inhibited total expression in the VTA, and induced translocation of DORs to neuronal membranes in the NAc. Conclusion: These findings demonstrate that MStim modulates neuron firing and DA release in the mesolimbic DA system through endogenous opioids and acetylcholine in the NAc. These findings demonstrate the need to explore more broadly the extra-somatosensory effects of peripheral mechanoreceptor activation and the specific role for mechanoreceptor-based therapies in the treatment of substance abuse.

Role of Lateral Hypothalamus in Acupuncture Inhibition of Cocaine Psychomotor Activity

“…Further, we have demonstrated that mechanical activation of this neuronal pathway, though the dorsal column-medial lemniscus pathway, elicits the same responses. Additionally, these effects can be blocked by inactivation of nicotinic acetylcholine and delta-opioid receptors in the NAc, suggesting a role for cholinergic interneurons in the NAc [ 24 ]. Thus, we suggest that a long-lasting decrease in cocaine locomotion by HT7 acupuncture would be due to modulation of neurotransmitters such as β-endorphin, GABA, acetylcholine, and DA in VTA and NAc.…”

Effect of Resonant Frequency Vibration on Delayed Onset Muscle Soreness and Resulting Stiffness as Measured by Shear-Wave Elastography

“…To date, pain relieving effects of vibration are most commonly attributed to the gate-control theory via the stimulation of somatosensory afferents; however, supraspinal mechanisms may be involved [60]. Recent studies have reported a decrease in gamma aminobutyric acid neuron firing activity [64] and an increase in dopamine neuron firing rates [65] in the ventral tegmental area of the brain in response to approximately 50 Hz. While these studies suggest vibration can modulate supraspinal central nervous system substrates, greater work is needed to better elucidate how they affect descending nociceptive influence.…”

Nociceptive stimuli activate the hypothalamus-habenula circuit to inhibit the mesolimbic reward system

“…Cumulative evidence has suggested that the reward system links to external somatosensory system [24, 25]. Somatosensory stimuli such as noxious stimulation influence the activity of DAergic neurons in the reward system [24].…”

“…Somatosensory stimuli such as noxious stimulation influence the activity of DAergic neurons in the reward system [24]. Activation of cervical spine mechanoreceptors modulates firing of VTA GABA neurons and dopamine release [25]. Furthermore, we and others have shown that somatosensory stimuli reduce drug-induced craving behaviors through modulating the mesolimbic DA systems in rats [26, 27].…”