Smoking is Associated with Reduced Leptin and Neuropeptide Y Levels and Higher Pain Experience in Patients with Fibromyalgia

Abstract

Smoking deregulates neuroendocrine responses to pain supporting production of neuropeptide Y (NpY) by direct stimulation of nicotinic receptors or by inhibiting adipokine leptin. Present study addressed the effect of cigarette smoking on adipokines and pain parameters, in 62 women with fibromyalgia (FM) pain syndrome with unknown etiology. Pain was characterized by a visual analogue scale, tender point (TP) counts, pressure pain threshold, and neuroendocrine markers NpY and substance P (sP). Levels of IGF-1, leptin, resistin, visfatin, and adiponectin were measured in blood and cerebrospinal fluid. Current smokers (n = 18) had lower levels of leptin compared to ex-smokers (n = 25, P = 0.002), while the expected NpY increase was absent in FM patients. In smokers, this was transcribed in higher VAS-pain (P = 0.04) and TP count (P = 0.03), lower pain threshold (P = 0.01), since NpY levels were directly related to the pain threshold (rho = 0.414) and inversely related to TP counts (rho = −0.375). This study shows that patients with FM have no increase of NpY levels in response to smoking despite the low levels of leptin. Deregulation of the balance between leptin and neuropeptide Y may be one of the essential mechanisms of chronic pain in FM.

Modulation of neural regulators of energy homeostasis, and of inflammation, in the pups of mice exposed to e-cigarettes

“…NPY is a potent stimulator of feeding and principally produced in the arcuate nucleus of the hypothalamus. NPY production is suppressed by cigarette smoke exposure (SE) as well as postsynaptic NPY Y1 receptor levels leading to anorexia and weight loss [11,24]; whereas smoking cessation was shown to increase NPY production resulting in overeating and weight gain [3,20].…”

Circulating leptin and pain perception among tobacco-dependent individuals

“…As reviewed in the introduction, leptin appears to be critical in the development of allodynia and it may contribute to the development of neuropathic pain (Maeda et al, 2009). Some have suggested that a decoupling of leptin and neuropeptide Y signaling may account for the higher pain report in smokers with fibromyalgia (Bokarewa, Erlandsson, Bjersing, Dehlin, & Mannerkorpi, 2014). Again the lack of human studies requires that existing animal literature guide the interpretation of these results.…”

Transmission pathways and mediators as the basis for clinical pharmacology of pain

“…Perhaps more interestingly, as the pain level (as judged by two different pain score systems) increased, the concentration of NPY showed concomitant increase [141]. A study by Bokarewa et al [142] evaluated the role of tobacco (cigarette smoking) in women with fibromyalgia. Interestingly, the women who smoked reported significantly higher levels of pain [142].…”

“…A study by Bokarewa et al [142] evaluated the role of tobacco (cigarette smoking) in women with fibromyalgia. Interestingly, the women who smoked reported significantly higher levels of pain [142]. At the same time, these women who smoked were found to have altered levels of leptin and NPY [142].…”

“…Interestingly, the women who smoked reported significantly higher levels of pain [142]. At the same time, these women who smoked were found to have altered levels of leptin and NPY [142]. …”