Attenuated pain response of obese mice (B6.Cg-lep) is affected by aging and leptin but not sex

Rodgers, Helen M.; Liban, Suadi; Wilson, Linda M.

doi:10.1016/j.physbeh.2013.10.007

Cited by 17 publications

(14 citation statements)

References 39 publications

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“…This alteration, and the ensuing disinhibition of vlPAG output neurons, is at the basis of the hypoalgesic behavior of obese (ob/ob) mice and explains the recent observation, published during the preparation of this manuscript, that attenuated pain response of these mice is affected by leptin (Rodgers et al, 2014). More importantly, these observations provide a possible mechanism for the different pain perception thresholds often observed in patients with obesity or eating disorders, in which leptin signaling is disrupted.…”

Section: Discussionmentioning

confidence: 67%

“…Eating disorders and obesity are accompanied by altered pain perception (Lautenbacher et al, 1990;Papežová et al, 2005;Foo and Mason, 2009;Rodgers et al, 2014). Although this phenomenon might be a consequence of changes in the hypothalamic-pituitary-adrenal (HPA) axis, stress response, and related or unrelated endocrine modifications (Lewis et al, 1980), its exact underlying mechanisms have not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Orexin-A and Endocannabinoid Activation of the Descending Antinociceptive Pathway Underlies Altered Pain Perception in Leptin Signaling Deficiency

Cristino

Luongo

Imperatore

et al. 2015

Neuropsychopharmacol

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Pain perception can become altered in individuals with eating disorders and obesity for reasons that have not been fully elucidated. We show that leptin deficiency in ob/ob mice, or leptin insensitivity in the arcuate nucleus of the hypothalamus in mice with high-fat diet (HFD)-induced obesity, are accompanied by elevated orexin-A (OX-A) levels and orexin receptor-1 (OX1-R)-dependent elevation of the levels of the endocannabinoid, 2-arachidonoylglycerol (2-AG), in the ventrolateral periaqueductal gray (vlPAG). In ob/ob mice, these alterations result in the following: (i) increased excitability of OX1-R-expressing vlPAG output neurons and subsequent increased OFF and decreased ON cell activity in the rostral ventromedial medulla, as assessed by patch clamp and in vivo electrophysiology; and (ii) analgesia, in both healthy and neuropathic mice. In HFD mice, instead, analgesia is only unmasked following leptin receptor antagonism. We propose that OX-A/endocannabinoid cross talk in the descending antinociceptive pathway might partly underlie increased pain thresholds in conditions associated with impaired leptin signaling.

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Section: Discussionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Orexin-A and Endocannabinoid Activation of the Descending Antinociceptive Pathway Underlies Altered Pain Perception in Leptin Signaling Deficiency

Cristino

Luongo

Imperatore

et al. 2015

Neuropsychopharmacol

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“…Genetic models of obesity present similar phenotypes to those described in alimentary obesity models (3.5.1). For noxious heat, both increased ( Cristino et al, 2016 , Rodgers et al, 2014 , Rossi et al, 2019 , Sugimoto et al, 2008 ), unaltered ( Iannitti et al, 2012 , Sugimoto et al, 2008 , Watson et al, 2014 ) and decreased ( Latham et al, 2009 , Roane and Porter, 1986 , Sugimoto et al, 2008 ) latencies were reported. Again, differences across studies might be explained, at least in part, by the time course of the pathology.…”

Section: Resultsmentioning

confidence: 99%

Diet, body weight and pain susceptibility – A systematic review of preclinical studies

Miranda

Campos

Leite‐Almeida

2021

Neurobiology of Pain

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Highlights Obesity has been associated with increased susceptibility to chronic pain. Dietary and genetic models of obesity have been used to study this association. Allodynia is a common finding but alterations in nociception were inconsistent across studies. In subacute/chronic models, nocifencive behaviors were increased and/or sustained. Reviewed studies are overall consonant with the clinical literature.

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“…An animal study demonstrated that leptin was involved in the development of allodynia and exacerbation of neuropathic pain [16]. Other studies conducted on animals have shown that leptin mediates nociceptive behavior [9] and alters nociceptive response [17]. It has been reported that leptin increases pain sensitivity [18, 19], and leptin-deficient mice have low pain sensitivity [16] although the mechanism of this effect remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Preoperative Serum Leptin Level Is Associated with Preoperative Pain Threshold and Postoperative Analgesic Consumption in Patients Undergoing Cesarean Section

et al. 2019

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Objective: This study aimed to investigate the preoperative level of serum leptin in cesarean section (C-section) patients with and without acute labor pain and its association with postoperative analgesic consumption and preoperative pain threshold. Materials and Methods: Preoperative leptin levels, preoperative pain threshold, postoperative analgesic consumption in the first 24 h, and postoperative pain severity (visual analog scale (VAS) scores at 1, 2, 4, 6, 12, and 24 h postoperatively) in C-section patients with labor pain (emergency C-section; n = 21) and without labor pain (elective C-section; n = 25) were compared. Results: There were no signiﬁcant differences between the groups regarding the demographic characteristics. Leptin levels, postoperative VAS scores, and analgesic consumption were significantly higher in the group with labor pain, while the preoperative pain threshold was lower. Serum leptin levels correlated negatively with pain threshold and positively with postoperative analgesic consumption. Multiple linear regression analyses in our study revealed that the preoperative leptin levels and having an emergency C-section independently affected the postoperative analgesic consumption and preoperative pain threshold, whereas their combined effects on these parameters were statistically not significant. Conclusion: Preoperative levels of serum leptin were higher in C-section patients with labor pain than in those without labor pain, and increased serum leptin levels were associated with decreased preoperative pain threshold and increased postoperative analgesic consumption in our study population. Postoperative analgesic requirements may vary among patients, and their requirements might be predicted using preoperative indicators. Serum levels of leptin might be one such indicator and this warrants further studies with larger sample sizes.

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Attenuated pain response of obese mice (B6.Cg-lep) is affected by aging and leptin but not sex

Cited by 17 publications

References 39 publications

Orexin-A and Endocannabinoid Activation of the Descending Antinociceptive Pathway Underlies Altered Pain Perception in Leptin Signaling Deficiency

Orexin-A and Endocannabinoid Activation of the Descending Antinociceptive Pathway Underlies Altered Pain Perception in Leptin Signaling Deficiency

Diet, body weight and pain susceptibility – A systematic review of preclinical studies

Preoperative Serum Leptin Level Is Associated with Preoperative Pain Threshold and Postoperative Analgesic Consumption in Patients Undergoing Cesarean Section

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