Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162473 (Frey)
 2,599 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The endogenous peptide bradykinin is found in plasma and inflammatory exudates and has been implicated as a chemical mediator of inflammatory pain and hyperalgesia. Two subtypes of bradykinin receptors, B1 and B2, have been described, and antagonists for the receptor subtypes have been synthesized. The bradykinin analogs [desArg9,Leu8]BK and DArg[Hyp3,DPhe7]BK have been reported to have antagonist activity at the B1 and B2 bradykinin receptors in smooth muscle, respectively. Behavioral studies in rats indicate that the bradykinin analogs can block the algesic effects of bradykinin. We wished to determine the effects of bradykinin and the bradykinin analogs (B1 and B2 analogs, respectively) on cutaneous nociceptors in the monkey. In addition, we wished to determine the type of bradykinin receptor that mediates the sensitizing effects of bradykinin. Recordings were made from single C-fiber and A-fiber nociceptive afferents (CMHs and AMHs) that innervated hairy skin. Heat sensitivity before and after the injections was determined with a heat test sequence consisting of stimuli that ranged, in 1 degree C increments, from 41 degrees to 49 degrees C. Intradermal injections of vehicle (neutral normal saline) failed to alter the heat response of CMHs. Bradykinin (10 nmol in 10 microliters) evoked activity in 6 of 10 CMHs and sensitized all the fibers to heat stimuli. After the bradykinin injection, the mean heat threshold of the CMHs decreased from 44 +/- 0.5 degrees to 42.7 +/- 0.5 degrees C (mean +/- SEM, p less than 0.02), and the total response to the heat test sequence increased by 87% (p less than 0.002). In a related psychophysical study in human volunteers, the same dose of bradykinin resulted in a comparable (115%) increase in ratings of pain (Manning et al., 1991). Bradykinin also evoked activity in 10 of 17 AMHs and sensitized 8 AMHs to heat stimuli. Bradykinin failed to alter the threshold for activation of CMHs to mechanical stimuli as measured by application of von Frey hairs to the receptive field. In contrast to bradykinin, intradermal injection of the B1 and B2 analogs (10 nmol in 10 microliters) evoked activity in 2 of 6 and 0 of 5 CMHs, respectively. A noteworthy finding was that both analogs enhanced the response of CMHs to heat stimuli by 50% (B1 analog, 1.5 +/- 0.1; B2 analog, 1.5 +/- 0.2). The B1 (n = 10) and B2 (n = 5) analogs did not evoke activity in any of the 15 AMHs tested.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The effects of bradykinin and sequence-related analogs on the response properties of cutaneous nociceptors in monkeys. 132 2

The function of the somatosensory system in patients with painful temporomandibular disorders is still a matter of discussion. We wished to determine cutaneous sensitivity to innocuous mechanical stimuli in the orofacial region before, during (3 and 12 min) and after standardized experimental jaw-muscle pain. Twelve healthy subjects were exposed to tonic infusion of hypertonic (5%) and isotonic (0.9%) saline into the masseter muscle. All subjects experienced moderate pain with hypertonic saline, and the area of self-reported pain increased significantly from 3 min after infusion start to 12 min after infusion start (mean +/- SEM: 115+/-49%; P < 0.05). The psychophysical ratings of punctate von Frey hair stimulation were significantly increased 12 min after start of hypertonic saline infusion as compared to baseline and post-baseline ratings at the site of infusion (50+/-10%; P < 0.05) and at two adjacent facial sites (18+/-7%, 37+/-9%; P < 0.05). In contrast, isotonic saline infusion was associated with a significant decrease in ratings at post-baseline as compared to baseline ratings. The psychophysical ratings of a stroking cotton swab stimulation were not significantly affected by infusion of saline. These results in a human model of jaw-muscle pain are comparable to animal studies demonstrating increased size of cutaneous receptive fields and increased responsiveness of brain stem neurons to cutaneous mechanical stimuli. Similar hyperexcitability changes may be part of the pathophysiological mechanisms involved in painful temporomandibular disorders.
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PMID:Mechanical hyperesthesia of human facial skin induced by tonic painful stimulation of jaw muscles. 951 65

In the this study we have investigated the threshold plasma concentration of lidocaine for reversal of mechanical 'allodynia' in a neuropathic pain model in the rat, defined the concentration-dependent limits of that reversal and compared the acute reversal during intravenous drug infusion with the persistent relief of allodynia assayed 48 h later. Actions of i.v. lidocaine on ipsilateral and contralateral legs were also assessed. Forty rats were sorted into five groups (n = 7-10) and underwent spinal root (L5-6) ligation to produce allodynia, as quantified by a lower force of von Frey hairs at the plantar hindpaw required to elicit paw withdrawal (PWT, paw withdrawal threshold). During surgery, intravenous catheters were placed for programmed lidocaine infusion and in some animals arterial catheters were also inserted for assaying lidocaine blood levels. PWTs were measured in ipsilateral and contralateral paws before and after ligation and during infusions which, beginning at 5 days after surgery, were conducted every other day to incrementing levels (1.1-9.7 microg/ml plasma). Ligation produced allodynia in ipsilateral paws (PWT = 1.22 +/- 0.42 g (+/-SEM)) and in contralateral paws (PWT = 4.99 +/- 0.61 g), both markedly lower than pre-operative control values for either paw (11.31 +/- 0.41 g). The ipsilateral allodynia was partially, but significantly and permanently reversed (to PWT = 6-8 g) after a lidocaine infusion to 2.1 microg/ml in two separate groups (n = 7, 8). Lower concentrations resulted in elevation of PWT during infusion but no sustained relief. The elevation of PWT during infusion at this threshold level among individual animals was positively correlated with the relief measured 48 h later, but higher lidocaine concentrations infused in subsequent dosings could exact no further sustained relief. The residual PWT level, after reversal by threshold lidocaine and greater, was constant for each individual rat tested over the next 14 days but varied substantially among individuals; some were restored to pre-operative PWTs and some were totally unresponsive to drug. Retrospective analysis revealed a significant and unanticipated correlation between the incidence of low pre-operative PWTs (< 10 g) and a lack of sustained reversal of post-operative allodynia by lidocaine. Contralateral allodynia, despite its acute reversal during infusion to 2.1 microg/ml and higher, was not persistently relieved after infusion of lidocaine to any concentration. Repeated infusions to subthreshold levels (<2 microg/ml) did not provide persisting relief of allodynia on either side, and infusions of saline were impotent. These findings show that experimental allodynia results from multiple factors, only some of which are sensitive to lidocaine treatment, and that prolonged reversal of allodynia is limited in extent and likely influenced by pre-existing factors.
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PMID:Differential efficacy of intravenous lidocaine in alleviating ipsilateral versus contralateral neuropathic pain in the rat. 1034 13

Electroacupuncture has been proposed to be a low cost and practical method that allows effective pain management with minimal collateral effects. In this study we have examined the effect of electroacupuncture against the hyperalgesia developed in a model of post-incisional pain in rats. A 1-cm longitudinal incision was made through the skin and fascia of the plantar region of the animal hind paw. Mechanical hyperalgesia in the incision was evaluated 135 min after the surgery with von Frey filaments. The tension threshold was reduced from 75 g (upper limit of the test) to 1.36 +/- 0.36 g (mean +/- SEM) in control rats. It is shown that a 15-min period of electroacupuncture applied 120 min after surgery to the Zusanli (ST36) and Sanyinjiao (SP6) points, but not to non-acupoints, produces a significant and long-lasting reduction of the mechanical hyperalgesia induced by the surgical incision of the plantar surface of the ipsilateral hind paw. The tension threshold was reduced from 75 to 27.6 +/- 4.2 g in animals soon after the end of electroacupuncture. The mechanical threshold in this group was about 64% less than in control. Electroacupuncture was ineffective in rats treated 10 min earlier with naloxone (1 mg/kg, ip), thus confirming the involvement of opioid mechanisms in the antinociceptive effects of such procedure. The results indicate that post-incisional pain is a useful model for studying the anti-hyperalgesic properties of electroacupuncture in laboratory animals.
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PMID:Anti-hyperalgesic effect of electroacupuncture in a model of post-incisional pain in rats. 1092 Apr 38

The aim of the study was to evaluate post-operative pain and analgesic use after pre-operative or post-incisional i.v. fentanyl plus low dose i.v. ketamine vs. a standard treatment receiving i.v. fentanyl but not ketamine. Men undergoing radical prostatectomy under general anesthesia were randomly assigned in a double-blinded manner to one of three groups. Patients received i.v. fentanyl before incision followed by an i.v. bolus dose (0.2 ml kg(-1)) and an i.v. infusion (0.0025 ml kg(-1)min(-1)) of 1 mg ml(-1) ketamine (group 1) or normal saline (groups 2 and 3). Seventy minutes after incision, patients received i.v. fentanyl followed by an i.v. bolus dose (0.2 ml kg(-1)) and an i.v. infusion (0.0025 ml kg(-1)min(-1)) of saline (groups 1 and 3) or ketamine (group 2). Pain, von Frey pain thresholds, and cumulative morphine consumption using patient-controlled analgesia (PCA) were assessed up to 72 h after surgery. 143 patients completed the study (group 1, n = 47, group 2, n = 50, group 3, n = 46). Cumulative PCA morphine (mean+/-SD) did not differ significantly among groups (group 1, 92.3+/-45.9 mg; group 2, 107.2+/-58.4 mg; group 3, 103.6+/-50.4 mg; P = 0.08 for groups 1 vs. 2, and groups 1 vs. 3). On day 3, the hourly rate (mean+/-SEM) of morphine consumption was significantly lower (p < 0.0009) in group 1 (0.61+/-0.013 mg h(-1)) than group 2 (0.86+/-0.011 mg h(-1)) and group 3 (0.89+/-0.008 mg h(-1)). Pain scores and von Frey pain thresholds did not differ significantly among groups. Two-week and 6-month follow-ups did not reveal significant group differences in pain incidence, intensity, disability or mental health. Pre-operative, low-dose administration of i.v. ketamine did not result in a clinically meaningful reduction in pain or morphine consumption when compared with post-incisional administration of ketamine or a saline control condition.
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PMID:Pre-emptive analgesia using intravenous fentanyl plus low-dose ketamine for radical prostatectomy under general anesthesia does not produce short-term or long-term reductions in pain or analgesic use. 1528 12