PubMed · 15729974
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F Magora. 2005. Procedural sedation.. https://pubmed.ncbi.nlm.nih.gov/15729974/
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1-Benzyl-5-aryltetrazoles were discovered to be novel antagonists for the P2X(7) receptor. Structure-activity relationship (SAR) studies were conducted around both the benzyl and phenyl moieties. In addition, the importance of the regiochemical substitution on the tetrazole was examined. Compounds were evaluated for activity to inhibit calcium flux in both human and rat recombinant P2X(7) cell lines using fluorometric imaging plate reader technology. Analogues were also assayed for their ability to inhibit IL-1beta release and to inhibit P2X(7)-mediated pore formation in human THP-1 cells. Compound 15d was advanced to efficacy studies in a model of neuropathic pain where significant reversal of mechanical allodynia was observed at doses that did not affect motor coordination.
A familial case of limb pain is described. Frequent vascular pain appeared during early childhood in affected individuals, often with predominance in the lower extremities. This pain subsided in patients during adolescence, when they began to suffer from typical migraine. The limb pain was moderate to severe, and refractory to analgesic and anti-migraine medications. Limb temperature was cold at the onset of pain, and became warm during the painful attacks. Plasma substance P and calcitonin gene-related peptide were elevated during the episodic pain. We propose this condition is a new precursor etiology of migraine, with possible autosomal dominant inheritance.
A pressure analgesiometric device was developed for unrestrained cats. Eleven cats were studied. Stimulation was via three rounded pins within a bracelet on the forearm. The pins were advanced by manual bladder inflation. Bladder pressure was measured using a strain gauge pressure transducer. The threshold was recorded at the behavioural end point. Thresholds were measured at 5 and 15min intervals for 2-4h, after removal/replacement of the cuff, for 120min after SC butorphanol (0.4mg/kg), and with mild skin inflammation at the testing site. Data were analysed using ANOVA. Pressure thresholds in untreated cats were around 150mmHg. The minimum interval for testing was established as 15min. Data were reproducible over 4h and beyond 24h. Thresholds in 5 cats increased (P<0.05) above baseline for 45min after butorphanol with a maximum increase of 270+/-182mmHg at 10min. Thresholds decreased with inflammation. The method appears suitable for feline analgesia investigations.