Amplified pain perception in patients with diabetic neuropathy is associated with altered serum calcitonin gene related peptide (CGRP)

Résumé

Introduction: Diabetic polyneuropathy (DPN) is the most common complication of diabetes mellitus, affecting up to 50% of patients whose first symptom is usually a painful sensation. The DPN among the other micro-vascular complications of diabetes mellitus is the major cause of death in these patients. Diabetes mellitus is associated with cardiovascular diseases with risk factors like dyslipidaemia, endothelial dysfunction, inflammation, vascular wall abnormalities and oxidative stress leading to vasoconstriction, been one of the hypothetical cause of DPN. Calcitonin gene-related peptide (CGRP) is the most potent micro-vascular vasodilator currently known. This study evaluates the relationship between serum level of CGRP in DPN patients and their level of pain perception.

Materials and method: Sixty volunteers were recruited for the study and divided into groups A and B. Group A consisted of 30 healthy volunteers who were randomly selected in the community. Group B was made up of 30 volunteer patients who presented with DPN having minimum of two symptoms (pain plus any other) and diagnosed (using Biothesiometer) at the diabetic clinic in Ekiti-State University Teaching Hospital, Ado-Ekiti, Ekiti-State. All subjects were trained and informed consents were obtained. They all underwent the sub-maximal effort tourniquet test, blood sample were taken and serum separated for the analysis of CGRP. Independent-Sample t-test was used to analyse the results and significance level was at p < 0.05.

Result: The time of pain tolerance was significantly lower in DPN (42.68±1.91 seconds) compared to control group (61.80±3.21 seconds). Serum level of CGRP (97.89±1.84) in DPN patients was significantly lower compared to control group (146.07±5.63).

Conclusion: This study has shown that patients with DPN are more susceptible to pain, which may be associated with lower levels of Calcitonin Gene Related Peptide. Thus there is an inverse relationship between diabetic peripheral neuropathic pain and CGRP

Keywords: Diabetic polyneuropathy, dyslipidaemia, endothelial dysfunction, inflammation

Résumé
Introduction : La polyneuropathie diabétique (DPN) est la complication la plus courante du diabète sucré affectant jusqu’à 50% des patients dont le premier symptôme est généralement une
sensation douloureuse. Le DPN parmi les autres complications micro-vasculaires du diabète sucré est la principale cause de décès chez ces patients. Le diabète sucré est associé à des maladies cardiovasculaires présentant des facteurs de risque tels que la dyslipidémie, le  dysfonctionnement endothélial, l’inflammation, les anomalies de la paroi vasculaire et le stress oxydatif conduisant à unevasoconstriction, constituant l’une des causes hypothétiques de la DPN. Le peptide associé au gène de la calcitonine (CGRP) est le vasodilatateur micro-vasculaire le plus puissant actuellement connu. Cette étude évalue la relation entre le taux sérique de CGRP chez les patients atteints de DPN et leur niveau de perception de la douleur.

Matériel et méthode : Soixante volontaires ont été recrutés pour l’étude et répartis en groupes A et B. Le groupe A était constitué de 30 volontaires en bonne santé choisis au hasard dans la
communauté. Le groupe B était composé de 30 patients volontaires présentant une DPN d’au moins deux symptômes (douleur et tout autre) et diagnostiqués (à l’aide d’un bio-thésiomètre) à la clinique diabétique de l’Hôpital d’Enseignement Universitaire de l’Etat d’Ekiti, AdoEkiti, l’Etat d’Ekiti. Tous les sujets ont été formés et des consentements éclairés ont été obtenus. Ils ont tous subi le test de garrot sous-maximal, des échantillons de sang ont été prélevés et le sérum séparé pour l’analyse du CGRP. Le test t pour échantillon indépendant a été utilisé pour analyser les résultats et le niveau de signification était à p dd 0,05.

Résultat : Le temps de tolérance à la douleur était significativement plus bas dans le DPN (42,68 ± 1,91 seconde) que chez le groupe témoin (61,80 ± 3,21 secondes). Le taux sérique de CGRP (97,89 ± 1,84) chez les patients atteints de DPN était significativement inférieur par rapport au groupe témoin (146,07 ± 5,63).

Conclusion: Cette étude a montré que les patients atteints de DPN sont plus sensibles à la douleur, ce qui peut être associée à des taux plus faibles de peptide lié au gène de la calcitonine. Il existe donc une relation inverse entre douleur neuropathique périphérique diabétique et CGRP.

Mots clés: Polyneuropathie diabétique, dyslipidémie, dysfonctionnement endothélial, inflammation

Correspondence: Dr. B.V. Owoyele, Department of Physiology, University of Ilorin, Ilorin, Nigeria. E-mail: deleyele@yahoo.com

pdf (anglais)

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