Sex differences in neuropathic pain in longstanding diabetes: Results from the Canadian Study of Longevity in Type 1 Diabetes

Cardinez, Nancy; Lovblom, Leif E.; Bai, Johnny-Wei; Lewis, Evan J.H.; Abraham, Alon; Scarr, Daniel; Boulet, Geneviève; Farooqi, Mohammed A.; Orszag, Andrej; Weisman, Alanna; Keenan, Hillary A.; Brent, Michael H.; Paul, Narinder; Bril, Vera; Cherney, David Z.I.; Perkins, Bruce A.

doi:10.1016/j.jdiacomp.2018.05.001

Cited by 22 publications

(11 citation statements)

References 25 publications

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“…Our findings align with a study of HFD obese mice, where sex impacted facial pain response to heat (Rossi et al, 2013), but differs from a rat study of a HFD-STZ model of T2D, which reported no sex differences in either mechanical, heat, or cold responses (Ferhatovic et al, 2013). With respect to human studies, our finding of shorter thermal latencies in female animals, a sign of hyperalgesia, correlate with clinical studies, where neuropathic pain is more frequent (Abraham et al, 2018, Abbott et al, 2011, Cardinez et al, 2018 or intense (Abraham et al, 2018) in females compared to males in T2D populations.…”

Section: Discussionsupporting

confidence: 77%

Sex differences in insulin resistance, but not peripheral neuropathy, in a diet-induced prediabetes mouse model

Elzinga

Savelieff

O’Brien

et al. 2021

Disease Models &Amp; Mechanisms

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Peripheral neuropathy (PN) is a common complication of prediabetes and diabetes and is an increasing problem worldwide. Existing PN treatments rely solely on glycemic control, which is effective in type 1 but not type 2 diabetes. Sex differences in response to anti-diabetic drugs further complicate the identification of effective PN therapies. Preclinical research has been primarily carried out in males, highlighting the need for increased sex consideration in PN models. We previously reported PN sex dimorphism in obese leptin deficient ob/ob mice. This genetic model is inherently limited, however, due to leptin's role in metabolism. Therefore, the current study goal was to examine PN and insulin resistance in male and female C57BL6/J mice fed a high-fat diet (HFD), an established murine model of human prediabetes lacking genetic mutations. HFD mice of both sexes underwent longitudinal phenotyping and exhibited expected metabolic and PN dysfunction compared to standard diet (SD) fed animals. Hindpaw thermal latencies to heat were shorter in HFD females versus HFD males, as well as SD females versus males. Compared to HFD males, female HFD mice exhibited delayed insulin resistance, yet still developed the same trajectory of nerve conduction deficits and intraepidermal nerve fiber density loss. Subtle differences in adipokine levels were also noted by sex and obesity status. Collectively, our results indicate that although females retain early insulin sensitivity upon HFD challenge, this does not protect them from developing the same degree of PN as their male counterparts.

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Section: Discussionsupporting

confidence: 77%

Sex differences in insulin resistance, but not peripheral neuropathy, in a diet-induced prediabetes mouse model

Elzinga

Savelieff

O’Brien

et al. 2021

Disease Models &Amp; Mechanisms

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“…In addition women are more susceptible to develop prevalent chronic conditions featuring pain as a symptom and there is both a higher sensitivity to and greater reporting of pain among women. For example, recent studies have confirmed sex differences in both the prevalence and the intensity of neuropathic pain in diabetes 9,10 , postoperative pain 11 , temporomandibular disorder 12 , pain in adolescents 13 and 'high-impact' chronic pain causing significant life interference 14 . In addition, a survey of the electronic medical records of 11,000 patients with pain uncovered significantly higher self-reported pain ratings in women compared with men across 14 different ICD-9 (International Classification of Diseases, ninth revision) diagnoses 3 .…”

mentioning

confidence: 99%

Qualitative sex differences in pain processing: emerging evidence of a biased literature

2020

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Although most patients with chronic pain are women, the preclinical literature regarding pain processing and the pathophysiology of chronic pain has historically been derived overwhelmingly from the study of male rodents. This Review describes how the recent adoption by a number of funding agencies of policies mandating the incorporation of sex as a biological variable into preclinical research has correlated with an increase in the number of studies investigating sex differences in pain and analgesia. Trends in the field are analysed, with a focus on newly published findings of qualitative sex differences: that is, those findings that are suggestive of differential processing mechanisms in each sex. It is becoming increasingly clear that robust differences exist in the genetic, molecular, cellular and systems-level mechanisms of acute and chronic pain processing in male and female rodents and humans.

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“…Moreover, 26% reported burning or aching pain in their feet or legs, indicating peripheral diabetic neuropathic pain. In a Canadian study of longevity in type 1 diabetes, the prevalence of neuropathic pain was 36%; only 8.9% of these used neuropathic pain medications and 16% used other pain medications [19]. Total bodily pain in the present study was associated with worse QoL in people with long‐term type 1 diabetes.…”

Section: Discussionmentioning

confidence: 52%

Higher levels of bodily pain in people with long‐term type 1 diabetes: associations with quality of life, depressive symptoms, fatigue and glycaemic control – the Dialong study

et al. 2020

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Aims To compare reported level of bodily pain, overall and health-related quality of life (QoL), depression and fatigue in people with long-term type 1 diabetes vs. a comparison group without diabetes. Further, to examine the associations of total bodily pain with QoL, depression, fatigue and glycaemic control in the diabetes group. Methods Cross-sectional study of 104 (76% of eligible) people with type 1 diabetes of ≥ 45 years' duration attending the Norwegian Diabetes Centre and 75 persons without diabetes who completed questionnaires measuring bodily pain (RAND-36 bodily pain domain), shoulder pain (Shoulder Pain and Disability Index), hand pain (Australian/Canadian Osteoarthritis Hand Index), overall QoL (World Health Organization Quality of Life-BREF), health-related QoL (RAND-36), diabetes-specific QoL (Audit of Diabetes-Dependent Quality of Life; only diabetes group), depression (Patient Health Questionnaire) and fatigue (Fatigue questionnaire). For people with type 1 diabetes, possible associations between the bodily pain domain (lower scores indicate higher levels of bodily pain) and other questionnaire scores, were measured with regression coefficients (B) per 10-unit increase in bodily pain score from linear regression. Results The diabetes group reported higher levels of bodily (P = 0.003), shoulder and hand pain (P < 0.001) than the comparison group. In the diabetes group, bodily pain was associated with lower overall and diabetes

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Sex differences in neuropathic pain in longstanding diabetes: Results from the Canadian Study of Longevity in Type 1 Diabetes

Cited by 22 publications

References 25 publications

Sex differences in insulin resistance, but not peripheral neuropathy, in a diet-induced prediabetes mouse model

Sex differences in insulin resistance, but not peripheral neuropathy, in a diet-induced prediabetes mouse model

Qualitative sex differences in pain processing: emerging evidence of a biased literature

Higher levels of bodily pain in people with long‐term type 1 diabetes: associations with quality of life, depressive symptoms, fatigue and glycaemic control – the Dialong study

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