Abstract
Systemic nitroglycerin (NTG) produces spontaneous-like migraine attacks in migraine sufferers and induces a condition of hyperalgesia in the rat 4 h after its administration. Endocannabinoid system seems to be involved in the modulation of NTG-induced hyperalgesia, and probably, in the pathophysiological mechanisms of migraine. In this study, the analgesic effect of anandamide (AEA) was evaluated by means of the formalin test, performed in baseline conditions and following NTG-induced hyperalgesia in male Sprague–Dawley rats. AEA was administered 30 min before the formalin injection. In addition, the effect of AEA (administered 30 min before NTG injection) was investigated on NTG-induced Fos expression and evaluated 4 h following NTG injection. AEA induced a significant decrease in the nociceptive behavior during both phases of the formalin test in the animals treated with vehicle, while it abolished NTG-induced hyperalgesia during the phase II. Pre-treatment with AEA significantly reduced the NTG-induced neuronal activation in nucleus trigeminalis caudalis, confirming the results obtained in our previous study, and in area postrema, while the same treatment induced an increase of Fos expression in paraventricular and supraoptic nuclei of the hypothalamus, parabrachial nucleus, and periaqueductal grey. The study confirms that a dysfunction of the endocannabinoid system may contribute to the development of migraine attacks and that a pharmacological modulation of CB receptors can be useful for the treatment of migraine pain.
Highlights
Alterations in the endocannabinoid levels have been found in animal models of pain, neurological and neurodegenerative states, disorders and inflammatory conditions [1, 2]
Pre-treatment with analgesic effect of anandamide (AEA) significantly reduced the NTG-induced neuronal activation in nucleus trigeminalis caudalis, confirming the results obtained in our previous study, and in area postrema, while the same treatment induced an increase of Fos expression in paraventricular and supraoptic nuclei of the hypothalamus, parabrachial nucleus, and periaqueductal grey
NTG induces a condition of hyperalgesia in the rat, through the activation of spinal and brainstem structures involved in nociception [13,14,15]; As such, NTG has been extensively used to investigate the neurobiological correlates of migraine pain, in rodents [13,14,15]; Recently, we have shown that NTG-induced hyperalgesia is associated with an alteration of endocannabinoid system (ECS) in some areas of rat brain [16]
Summary
Alterations in the endocannabinoid levels have been found in animal models of pain, neurological and neurodegenerative states, disorders and inflammatory conditions [1, 2]. There is strong evidence that cannabinoids (CB) can induce antinociceptive effects in models of phasic or tonic pain, through activation of CB receptors located on neurons both within and outside the brain and spinal cord [3]. It has been shown that CB suppress spinal Fos expression, a neurochemical marker of neuronal activation [4], in a variety of animal models of persistent pain [5, 6]. The role of the endocannabinoid system in the pathogenesis of headaches has been recently put under scrutiny. Migraine may be caused by cerebral vasodilatation or by abnormal neurological firing or by neurogenic dural inflammation [7].
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