Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pharmacological interest in the tripeptide thyrotropin-releasing hormone (TRH) is due to the multiple effects it produces. In fact, apart from taking part in regulating the activity of the hypothalamo-pituitary-thyroid axis, TRH produces various neuropharmacological effects which indicate a biological role that is probably more important than that of a releasing hormone. Trials performed in animals have shown, for example, the dose-dependent capacity of TRH to induce analgesia, probably by interacting with the opioid peptide system. Motor activity is affected by TRH. In fact this tripeptide elicits an increase in spontaneous motor and explorative activities by interacting with the dopaminergic neurotransmitter system at the nucleus accumbens level. The neuropharmacological activities of TRH include an interesting arousal effect and an analeptic action on generalized depression of the CNS whether this depression is of natural origin, such as hibernation, or induced pharmacologically (barbiturates, ethanol) or of a traumatic origin (coma). This analeptic action is attributable to stimulation of cholinergic neurons in the septo-hippocampal area and to the presence of terminals containing TRH in the lateral septum and TRH receptors concentrated especially in the medial septum and diagonal band of Broca. It has also been suggested that TRH localized in the pineal gland has a part in activating the neuronal mechanisms of arousal. Associated with the arousal effect and especially evident in variously originated shock conditions are the activating effects of TRH on vegetative functions (body temperature, circulation, the gastrointestinal tract). These stimulatory activities on the CNS were the rationale for therapeutic use of TRH in the initial treatment of coma due to brain trauma and for the treatment of endogenous depression. A most interesting property of TRH is that of counteracting the neurological deficit due to experimental lesion of the spinal cord particularly with regard to spasticity and ataxia. Electrophysiological trials have shown that TRH depolarizes the motoneurons in frog spinal cord thereby increasing the monosynaptic reflex. Furthermore, TRH has recently been shown to have a trophic effect on cultures of rat fetus spinal cord. On this basis TRH has been used successfully for the treatment of amyotropic lateral sclerosis (Charcot's syndrome) and spinocerebellar degeneration. Further support for this therapeutic strategy is given by the demonstration that deafferentiation of rat spinal cord produces an increased density of TRH spinal receptors. Recent studies have also given encouraging results on the possible therapeutic use of TRH for the treatment of Alzheimer's disease.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Pharmacologic profile of protirelin tartrate]. 212 84

The octapeptide form of CCK predominates in the central nervous system (CNS) of mammalian species, including man. Many of the physiological roles of CCK in the CNS are unknown, but it is believed to be involved in nociception. CCK is distributed throughout cortical grey matter, periaqueductal grey matter, ventromedial thalamus and spinal dorsal horn, all of which are areas known to be associated with pain modulation. CCK receptor subtypes have been identified and may be classified according to their affinity for the sulphated and desulphated forms of CCK-8 and the recently described selective antagonist. MK-329. CCK-A receptors have high affinity for sulphated CCK-8 and for MK-329 but low affinity for desulphated CCK-8 and CCK-4 whilst CCK-B sites bind MK-329 with low affinity and discriminate poorly between sulphated and desulphated CCK-8. CCK-A receptors are found predominantly in peripheral tissues but they also exist in discrete regions of the primate CNS, including the spinal cord. CCK-B receptors are found ubiquitously throughout other regions of the neuraxis. The results of studies on the effects of CCK-8 and the decapeptide analogue caerulein on pain thresholds are conflicting. Some workers suggest that large doses of CCK-8 and caerulein induce naloxone-reversible analgesia in certain pain models. However, it appears likely that analgesia induced by large doses of CCK and caerulein in animals may be a pharmacological rather than a physiological phenomenon. Accordingly, others have found that small (and most probably, physiological) doses of CCK-8 attenuate the analgesic effects of morphine, and of endogenous opioids. Thus, it has been proposed that CCK may act as an endogenous opiate antagonist. Studies in rats with the selective CCK antagonist MK-329 have helped clarify the interaction between CCK and morphine-induced analgesia. Treatment with MK-329 enhances morphine analgesia and chronic treatment with MK-329 prevents the development of tolerance to morphine analgesia. However, the antagonist does not prevent naloxone-precipitated withdrawal symptoms in morphine-dependent rats. In man, caerulein prevents pain associated with gall-bladder contraction, probably by relaxation of the sphincter of Oddi. Caerulein has also been shown to reduce renal colic and the pain of intermittent claudication. Preliminary clinical studies with the weak, non-selective, CCK antagonist proglumide, indicate an enhancement of morphine analgesia. As yet, no studies have demonstrated analgesic effects of CCK antagonists in man when administered alone.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:The role of CCK caerulein, and CCK antagonists in nociception. 269 75