Inheritable and acquired hyperalgesia associated to abnormal opioid receptor set-up seem to act as opiate addiction preventors.
Hyperalgesia is known to depend on neuroplastic changes chiefly represented by long-term potentiation. These phenomena are proved to depend on excitatory amino acids (EAAs) action at the level of NMDA receptors. This action is known to be related to nitric oxide (NO) release. We found a visceral/vascular hyperalgesia state in migraine (M) sufferers as well as an inheritable systemic hyperalgesia in healthy subjects who are first-degree consanguineous with M sufferers; this type was labelled 'third hyperalgesia'. We discovered that a hyper-increase of plasma L-citrulline, equimolar co-product in the synthesis of NO, characterizes both M sufferers and their first-degree relatives who are exempt from primary headache. A similar pattern never occurred in healthy subjects having both a personal and family history negative for primary headache. We conclude that both 'third hyperalgesia' and a pattern of NO synthase (NOS) hyperactivity seems to be inheritable and can constitute, at least in part, a ground for developing headache. Morphine, proved to be unable to relieve M attack, was given in low doses that caused pain and side-effects in M sufferers only. This outcome seemingly indicates that M sufferers are characterized by a set-up of opioid receptor subtypes different from that of healthy headache-exempts. Following a period of morphine addiction and a withdrawal period, 65.07% of a group of 63 opiate addicts developed M syndrome. All these subjects were first-degree consanguineous relatives of primary headache sufferers. Discussion topics concern the activity of morphine in NO release and the role of NO in sensory transmission of both controls and hyperalgesia sufferers. It is suggested that the inheritable couple consisting of hyperalgesia and NOS hyperactivity can play some role in setting off the pain occurring following morphine in M sufferers.
Nicolodi
M
M
Interuniversity Centre of Clinical Pharmacology and Neurochemistry of Idiopathic Headache, Florence, Italy.
Volpe
A R
AR
Del Bianco
P L
PL
Sicuteri
F
F
D000328:Adult; D015415:Biomarkers; D003241:Consanguinity; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D009293:Opioid-Related Disorders / Q000517:prevention & control*; D011957:Receptors, Opioid / Q000502:physiology*
D015415:Biomarkers; D011957:Receptors, Opioid