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

The neuropeptide neurotensin (NT) elicits hypothermic and naloxone-insensitive analgesic responses after brain injection. Recent pharmacological evidence obtained with NT agonists and antagonists suggests that these effects are mediated by a receptor distinct from the initially cloned high-affinity NT receptor (NTR1). The recent cloning of a second NT receptor (NTR2) prompted us to evaluate its role in NT-induced analgesia. Intracerebroventricular injections in mice of two different antisense oligodeoxynucleotides from the NTR2 markedly decreased NTR2 mRNA and protein and reduced NT-induced analgesia. This effect was specific, because NTR1 levels were unaffected, and sense or scramble oligodeoxynucleotides had no effect. Structure-activity studies revealed a close correlation between the analgesic potency of NT analogs and their affinity for the NTR2 and disclosed potent and selective agonists of this receptor. These data confirm that NTR1 is involved in the NT-elicited turning behavior and demonstrate that the NTR2 mediates NT-induced analgesia.
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PMID:Identification of the receptor subtype involved in the analgesic effect of neurotensin. 987 Sep 78

Neurotensin (NT) is an endogenous neuropeptide that exerts potent opioid-independent analgesic effects, most likely via the type 2 NT receptor (NTR2). Previous morphological and electrophysiological studies suggested that the NT-NTR2 system is primarily localized in structures that constitute the descending pain control pathway, such as the periaqueductal gray (PAG), the rostral ventromedial medulla (RVM), and the spinal dorsal horn (SDH). However, relevant morphological evidence for this neurotensinergic (NTergic) circuit is lacking. Thus, the aim of the present study was to morphologically elucidate the potential sites and connections in the NT-NTR2 system that are involved in the descending pain control pathway. Based on light and electron microscopy combined with anterograde and retrograde tracing, we found evidence that NTR2-immunoreactive (IR) neurons in the RVM receive NT-IR projections originating from the PAG; express NT, serotonin (5-HT), or both; and send projections that terminate in laminae I and II of the SDH. These results suggest that NTR2 may contribute to pain control by binding to NT in the PAG-RVM-SDH pathway. In conclusion, our data provide morphological evidence for an NTergic PAG-RVM-SDH pathway, implicating novel mechanisms of NT-induced analgesia.
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PMID:Morphological evidence for a neurotensinergic periaqueductal gray-rostral ventromedial medulla-spinal dorsal horn descending pathway in rat. 2534 62