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Vitamin A active metabolite, all-trans retinoic acid, induces spinal cord sensitization. I. Effects after oral administration.

ABSTRACT: BACKGROUND AND PURPOSE: Retinoic acid is an active metabolite of vitamin A involved in the modulation of the inflammatory and nociceptive responses. The aim of the present study was to analyze the properties of spinal cord neuronal responses of male Wistar rats treated with all-trans retinoic acid (ATRA) p.o. in the normal situation and under carrageenan-induced inflammation. We also studied the expression and distribution of cyclooxygenases (COX) in the spinal cord. EXPERIMENTAL APPROACH: Properties of spinal cord neurons were studied by means of the single motor unit technique. The expression of COX enzymes in the spinal cord was assessed by Western blot analysis and immunohistochemistry. KEY RESULTS: Intensity thresholds for mechanical and electrical stimulation (C-fibers) were significantly lower in animals treated with ATRA than vehicle, either in normal rats or in rats with inflammation. The size of cutaneous receptive fields was also larger in animals treated with ATRA in the normal and inflammatory conditions. The expression of COX-2 enzyme, but not COX-1, was significantly higher in animals treated with ATRA. COX-2 labeling was observed in dorsal horn cells and in ventral horn motoneurons. CONCLUSIONS AND IMPLICATIONS: In conclusion, the oral treatment with ATRA in rats induces a sensitization-like effect on spinal cord neuronal responses similar to that observed in animals with inflammation and might explain the enhancement of allodynia and hyperalgesia observed in previously published behavioral experiments. The mechanism of action involves an over-expression of COX-2, but not COX-1, in dorsal and ventral horn areas of the lumbar spinal cord.

SUBMITTER: Romero-Sandoval EA

PROVIDER: S-EPMC1629405 | biostudies-other | 2006 Sep

REPOSITORIES: biostudies-other

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Project description:BackgroundCentral sensitization is considered a key mechanism underlying neuropathic pain (NP) after spinal cord injury (SCI).MethodsTwo novel proxies for central sensitization were investigated in thoracic SCI subjects with (SCI-NP) and without NP (SCI-nonNP) compared to healthy controls (HC). Specifically, temporal summation of pain (TSP) was investigated by examining pain ratings during a 2-min tonic heat application to the volar forearm. Additionally, palmar heat-induced sympathetic skin responses (SSR) were recorded in order to reveal changes in pain-autonomic interaction above the lesion level. Pain extent was assessed as the percentage of the body area and the number of body regions being affected by NP.ResultsEnhanced TSP was observed in SCI-NP (+66%) compared to SCI-nonNP (-75%, p = 0.009) and HC (-59%, p = 0.021). In contrast, no group differences were found (p = 0.685) for SSR habituation. However, pain extent in SCI-NP was positively correlated with deficient SSR habituation (body area: r = 0.561, p = 0.024; body regions: r = 0.564, p = 0.023).ConclusionsThese results support the value of TSP and heat-induced SSRs as proxies for central sensitization in widespread neuropathic pain syndromes after SCI. Measures of pain-autonomic interaction emerged as a promising tool for the objective investigation of sensitized neuronal states in chronic pain conditions.SignificanceWe present two surrogate readouts for central sensitization in neuropathic pain following SCI. On the one hand, temporal summation of tonic heat pain is enhanced in subjects with neuropathic pain. On the other hand, pain-autonomic interaction reveals potential advanced measures in chronic pain, as subjects with a high extent of neuropathic pain showed diminished habituation of pain-induced sympathetic measures. A possible implication for clinical practice is constituted by an improved assessment of neuronal hyperexcitability potentially enabling mechanism-based treatment.

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Vitamin A active metabolite, all-trans retinoic acid, induces spinal cord sensitization. I. Effects after oral administration.

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