Effects of Glycemic Regulation on Chronic Postischemia Pain

Ross-Huot, Marie-Christine; Laferrière, André; Gi, Cho Min; Khorashadi, Mina; Schricker, Thomas; Coderre, Terence J.

doi:10.1097/aln.0b013e31822a63c9

Cited by 12 publications

(3 citation statements)

References 58 publications

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“…High blood glucose affects the protein expression levels of opioid receptors ( 10 , 11 ) and reduces the analgesic potential of opioid receptor agonists ( 12 , 13 ). Moreover, high blood glucose has pro-inflammatory, pro-oxidative, and pro-thrombotic properties, which may play a key role in enhancing hyperalgesia ( 14 ). Ion channels of nociception are upregulated, gamma-aminobutyric acid (GABA)ergic neurons are downregulated, and inhibitory pain signal transmission is weakened, resulting in double hyperalgesia ( 15 ).…”

Section: Discussionmentioning

confidence: 99%

The Relationship Between Pre-Operative Glycosylated Haemoglobin and Opioid Consumption After Caesarean Section in Women With Gestational Diabetes Mellitus

Yang

et al. 2022

Front. Endocrinol.

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IntroductionWomen with Gestational diabetes mellitus (GDM) had a higher need and consumption of analgesics than women without GDM. The preoperative level of HbA1c was associated with the postoperative consumption for analgesics in diabetic patients. This prospective observational study go further to investigate the relationship between the pre-operative HbA1c and the post-operative consumption for analgesics in women with GDM.MethodsWomen with GDM and a singleton pregnancy undergoing elective cesarean section under combined spinal-epidural anaesthesia were divided into two groups based on pre-operative HbA1c: group HbA1c < 6% and group HbA1c ≥ 6%. Analgesics consumption, number of patient-controlled analgesia (PCA) compression, and pain scores in 6 hours and 24 hours post-operation were compared between the two groups. Then Pearson’s correlation coefficient and a stepwise multivariate linear regression were performed to investigate possible independentpredictors of post-operative 24-hour sufentanil consumption.ResultsAnalgesics consumption was significantly lower (18.8 ± 0.4 vs 23.2 ± 4.3; 82.7 ± 2.4 vs 115.8 ± 17.4, P < 0.001), and number of PCA compressions was significantly less frequent (1 [1-2] vs 3 [1-5]; 5 [3-7] vs 7 [3-15], P < 0.001), and in group HbA1c < 6% than in group HbA1c ≥ 6% in 6 hours and 24 hours post-operation.The univariate analysis showed that sufentanil consumption at 24 hours post-operation was significantly related to pre-operative HbA1c (r = 0.338, P < 0.001) and parity (r = 0.184, P = 0.03) and was related to blood glucose management methods (r = 0.172, P = 0.043). Multivariate linear regression analysis showed that HbA1c was the independent factor related to post-operative 24-hour sufentanil consumption (adjusted r2 = 0.246, P < 0.001)ConclusionsThis study demonstrated that in pregnant women with GDM, the pre-operative HbA1c is independently related to the need for and consumption of analgesics in 24 hours after CS.

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Section: Discussionmentioning

confidence: 99%

The Relationship Between Pre-Operative Glycosylated Haemoglobin and Opioid Consumption After Caesarean Section in Women With Gestational Diabetes Mellitus

Yang

et al. 2022

Front. Endocrinol.

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“…infusion (0.15 ml/hour) of sodium pentobarbital (Ceva Santé Animale, Libourne, France) for 2 hr. One milliliter of Dextrose in water (40% w/v) was administered intraperitoneally every hour of the occlusive period, as hyperglycemia enhances CPIP mechanical allodynia (Ross‐Huot et al, ). Following induction of anesthesia, a Nitrile 70 Durometer O‐ring (O‐rings West, Seattle, WA cat # 76245–368) with an internal diameter of 5.5‐mm was slipped around the rat's left hind limb proximal to the ankle joint to effect a complete blockade of arterial blood flow.…”

Section: Introductionmentioning

confidence: 99%

Topical combination of meldonium and N‐acetyl cysteine relieves allodynia in rat models of CRPS‐1 and peripheral neuropathic pain by enhancing NO‐mediated tissue oxygenation

Fulas

Laferrière

Stein

et al. 2020

Journal of Neurochemistry

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Local microvascular dysfunction and consequent tissue ischemia/hypoxia contribute to the symptoms of complex regional pain syndrome (CRPS) and peripheral neuropathic pain. As nitric oxide (NO) is a key regulator of microvascular blood flow, compounds that increase it are potentially therapeutic for these pain conditions. This led us to hypothesize that the topical administration of drugs that modulate local tissue NO levels can alleviate the pain of CRPS and peripheral neuropathic pain. We investigated the anti‐allodynic effect of a combination of two NO‐modulating drugs: meldonium and N‐acetylcysteine (NAC). An equimolar topical formulation of the two drugs was tested on chronic post‐ischemic pain (CPIP), a rat model of CRPS, as well as chronic constriction injury (CCI) of the sciatic nerve and chemotherapy‐induced painful neuropathy (CIPN), rat models of peripheral neuropathic pain. Topical meldonium‐NAC produced significant anti‐allodynia in CPIP, CCI, and CIPN rats. Moreover repeated application of topical meldonium‐NAC produced an increase in the duration of anti‐allodynia in the CPIP and CCI rats. While pre‐treatment with an NO synthase inhibitor attenuated the anti‐allodynic effects of meldonium‐NAC, 30‐min hyperbaric oxygen treatment combined with a non‐effective dose of meldonium‐NAC produced significant anti‐allodynic effects in CPIP rats. Both experiments implicated NO in the drug combination's anti‐allodynic effects. To ascertain the role played by changes in local tissue NO, we performed a quantification of plantar muscle NO in CPIP rats after hind paw topical treatment with meldonium‐NAC and revealed significantly increased plantar muscle NO levels in drug‐treated rats. The drug combination also reversed the reduction in tissue oxygenation normally observed in CPIP hind paws. In addition to introducing a novel topical treatment for mechanical allodynia in CRPS and peripheral neuropathic pain, this work showcases the analgesic potential of locally targeting microvascular dysfunction and tissue ischemia/hypoxia in these conditions, with emphasis on the role of NO.

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“…Failure to provide bedding material for a rat to make a nest for her pups can lead to hyperalgesia in those pups when they become adults 55,56 , and the handling of young animals (for example, related to injections, and involving the stress of maternal separation) can cause long-term alterations in pain sensitivity 41,[57][58][59][60][61][62][63] . A growing literature also documents the effect of diet on pain sensitivity [64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80] . In one case, differences in the soy content of rat chow turned out to be wholly responsible for a failure to replicate in Baltimore the findings of studies originally performed in Jerusalem 65 .…”

Section: Jeffrey S Mogilmentioning

confidence: 99%

Laboratory environmental factors and pain behavior: the relevance of unknown unknowns to reproducibility and translation

Mogil

2017

Lab Anim

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Effects of Glycemic Regulation on Chronic Postischemia Pain

Cited by 12 publications

References 58 publications

The Relationship Between Pre-Operative Glycosylated Haemoglobin and Opioid Consumption After Caesarean Section in Women With Gestational Diabetes Mellitus

The Relationship Between Pre-Operative Glycosylated Haemoglobin and Opioid Consumption After Caesarean Section in Women With Gestational Diabetes Mellitus

Topical combination of meldonium and N‐acetyl cysteine relieves allodynia in rat models of CRPS‐1 and peripheral neuropathic pain by enhancing NO‐mediated tissue oxygenation

Laboratory environmental factors and pain behavior: the relevance of unknown unknowns to reproducibility and translation

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