Mechanical stimulation of cervical vertebrae modulates the discharge activity of ventral tegmental area neurons and dopamine release in the nucleus accumbens
BRAIN STIMULATION
Authors: Bills, Kyle B.; Obray, J. Daniel; Clarke, Travis; Parsons, Mandy; Brundage, James; Yang, Chae Ha; Kim, Hee Young; Yorgason, Jordan T.; Blotter, Jonathan D.; Steffensen, Scott C.
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 (45-80 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. (C) 2019 Published by Elsevier Inc.
Perineural invasion in intramedullary spinal cord metastasis
ANNALS OF THE ROYAL COLLEGE OF SURGEONS OF ENGLAND
Authors: Jayakumar, N.; Ismail, H.; Athar, S.; Ashwood, N.
Abstract
A woman in her late sixties was referred to the orthopaedic clinic with progressive lower limb weakness and gait disturbance. She was known to have breast cancer with pre-existing infiltrative disease in the left brachial plexus. Magnetic resonance imaging of the spine revealed an intramedullary spinal cord metastasis in the lower cervical cord at C6-C7. She underwent surgical excision but died within six weeks of surgery. This rare case of an intramedullary spinal cord metastasis highlights the extremely poor prognosis in this condition as well as the possibility of perineural invasion into the spinal cord from the brachial plexus lesion. A detailed discussion of the literature on intramedullary spinal cord metastases is also presented.