Journal
NEUROSCIENCE LETTERS
Volume 743, Issue -, Pages -Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2020.135566
Keywords
Nicotine; Smoking; Nicotinic acetylcholine receptor (nAchR); Chronic pain; Inflammatory factors (TNF alpha, COX2)
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Funding
- department of Anesthesiology, Perioperative Medicine and Pain Management, University of Miami Miller School of Medicine, USA
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This study found that chronic nicotine administration induces hypersensitivity to mechanical stimuli and decreases the pain perception threshold. Nicotine can alter the expression levels of alpha 7-nAChR in the brain and spinal cord, and selective agonists can reverse this hypersensitivity. Additionally, chronic nicotine administration leads to an increase in microglial cells and inflammatory factors in the spinal cord, potentially contributing to chronic pain.
Smokers have a higher incidence of chronic pain than non-smokers, but the neural mechanism is not yet fully understood. Nicotine is the main component of tobacco and acts as an agonist for nicotinic cholinergic receptors (nAChRs) in the nervous system. This study was approved by the IACUC of UM. The effects of chronic nicotine administration on mechanical sensitivity were studied using a rat model. The changes in the expression levels of the alpha 7 isoform of nAChR (alpha 7-nAChR), inflammatory cytokines TNF alpha and COX-2, as well as the density of neum-immune cells (astrocytes and microglia) were measured concurrently. The results indicate that long-term nicotine administration induces hypersensitivity to mechanical stimuli, as demonstrated by a significant reduction in the pain perception threshold. In response to nicotine, the expression levels of alpha 7-nAChR increased in the periaqueductal gray matter (PAG) and decreased in the spinal cord. Acute administration of the selective alpha 7-nAChR agonist CDP-Choline reversed this hypersensitivity. Chronic nicotine administration led to an increase of microglial cells in the dorsal horn of the spinal cord and increased expression levels of the cytokines TNF alpha and COX-2. This study suggests that decreased alpha 7-nAChR expression in the spinal cord, as a result of long-term exposure to nicotine, may be causatively linked to chronic pain. Simultaneously, the increase of neuro-immune factors in the spinal cord is also a potential factor leading to chronic pain.
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