Perineural resiniferatoxin prevents the development of hyperalgesia produced by loose ligation of the sciatic nerve in rats.

BACKGROUND: The vanilloid receptors (TRPV1) are found in peripheral nerve fibers; their stimulation by capsaicin leads to release of calcitonin gene-related peptide and other neuropeptides participating in neuroinflammation. On the other hand, various inflammatory mediators, released after nerve damage, can activate or sensitize the TRPV1 receptors. These findings together suggest a protective effect of TRPV1 receptor blockade in neuropathy. In the present study, we tested the hypothesis that perineural resiniferatoxin (RTX) can prevent the development of hyperalgesia caused by placing loosely constrictive ligatures around the sciatic nerve. METHODS: Male Sprague-Dawley rats received a single percutaneous injection of RTX (0.0005%, 0.1 mL) or vehicle at the sciatic nerve, and underwent surgery 3 h later to place four loose ligatures around the nerve on the side of drug administration. Responses to noxious heat (withdrawal latency, paw-lift duration), repetitive stimulation with von Frey filaments, and changes in hindpaw posture (toe spread, ventroflexion, and foot exorotation) were assessed. RESULTS: Perineural RTX administered before surgery completely prevented ligation-induced reduction in withdrawal latency, increase in paw lift duration and increase in withdrawal frequency to von Frey filaments. The preventive effect of RTX on the development of deficits in hindpaw posture was pronounced but not complete, e.g., on day 7 after surgery, the cumulative paw-posture score (0-6) was 1.69 +/- 0.92 with RTX and 4.06 +/- 1.68 with vehicle (P < 0.005). The effect of RTX used against the background of already developed neuropathy was limited to thermal hypoalgesia lasting for a relatively short period. CONCLUSION: Perineural RTX prevents the development of neuropathy caused by placing loosely constrictive ligatures on the sciatic nerve. Perioperative use of drugs acting via the TRPV1 receptors may hold the promise for preventing neuropathic pain after surgery on peripheral nerves.

Memory of pain: the effect of perineural resiniferatoxin.

The long-lasting imprint of acute pain in the central nervous system may contribute to the transition of acute pain to chronicity. The long-term potentiation (which is proposed as a mechanism of memory) and central sensitization were each reported as a form of synaptic plasticity, and both can be initiated by stimulation of C fibers. In the current study, we assessed nociceptive memory regarding hyperalgesia by measuring distant hyperalgesia after repeated carrageenan-induced inflammation. This approach was used to determine whether selective blockade of C fibers can prevent the development of a long-lasting imprint of hyperalgesia. In rat experiments, resiniferatoxin was administered percutaneously at the sciatic and saphenous nerves, and two crossover intraplantar injections of carrageenan into the hindpaws were performed 2 wk apart. Responses to noxious pressure and heat and changes in paw volumes were measured at various intervals during two carrageenan-induced inflammations. The experiments demonstrated that after recovery of hyperalgesia induced by the initial inflammation, repeated inflammation led to the development of a distant hyperalgesia that was absent during the initial inflammation. The maximum of distant hyperalgesia (decrease of noxious pressure threshold in the contralateral hindpaw from 141 +/- 23 g to 96 +/- 19 g; P < 0.0001) was reached 24 h after the second injection of carrageenan. The development of distant hyperalgesia during the repeated inflammation was completely prevented (P < 0.0002) by perineural resiniferatoxin (0.001%) administered before the initial injection of carrageenan. These results indicate that selective blockade of nociceptive fibers prevents formation of long-term hyperalgesia-related imprint in the central nervous system. Thus, pain memory can be preempted by selective and prolonged blockade of C-fibers.

Perineural resiniferatoxin prevents hyperalgesia in a rat model of postoperative pain.

Resiniferatoxin (RTX) is a vanilloid agonist with a unique spectrum of activities. Vanilloids bind to the transient receptor potential ion channel subtype 1, a nonselective cation ionophore important in the integration of different noxious signals. Vanilloid agonists selectively decrease sensitivity to noxious stimuli. In this study, we sought to determine whether perineural RTX prevents hyperalgesia in a model of incisional pain. In a rat model, RTX was administered percutaneously to the sciatic and saphenous nerves before the plantar incision. The withdrawal response to von Frey filaments, the struggle response to pressure on the paw, and pain scoring based on weight bearing were measured before RTX and at various intervals for 8 days after RTX. A percutaneous injection of RTX (0.0003%) to the sciatic (0.1 mL) and saphenous (0.05 mL) nerves completely prevented incisional hyperalgesia. Two hours after incision, the withdrawal threshold was 51 mN without and 456 mN with RTX (P < 0.0001). RTX also prevented the incision-induced decrease in struggle threshold and abolished the pain behavior associated with weight bearing. We conclude that RTX provides a type of neural blockade when postoperative pain is abolished and that nonpainful sensations and motor functions are preserved.

The double-density sign: a radiographic finding suggestive of an os acromiale.

BACKGROUND: An os acromiale results from the failure of fusion of the acromial secondary centers of ossification. It is most easily seen radiographically on an axillary lateral view. The purpose of the present study was to describe two simple radiographic findings, the double-density sign on a standard anteroposterior view of the shoulder and a cortical irregularity found on a supraspinatus outlet view, that are highly suggestive of an os acromiale. METHODS: Anteroposterior, axillary lateral, and supraspinatus outlet radiographs of thirty-four shoulders in thirty adult patients with an os acromiale were reviewed by two independent observers and were compared with those of a control group of thirty-one shoulders in twenty-nine patients without an os acromiale. Statistical analysis was performed with use of a generalized logistic regression model to determine if an os acromiale could be detected on all three radiographic views. A kappa analysis was performed to determine interobserver reliability. RESULTS: In the group with an os acromiale, twenty-eight shoulders had a meso-acromion and six had a pre-acromion. A double-density sign was noted on the anteroposterior radiograph of 82.4% of the shoulders, an os acromiale was noted on the axillary lateral radiograph of 95.6% of the shoulders, and a cortical irregularity was noted on the supraspinatus outlet radiograph of 75.8% of the shoulders. In the control group, a double-density sign was noted on the anteroposterior radiograph of 4.8% of the shoulders, no os acromiale was seen on the axillary lateral radiograph of any of the shoulders, and a cortical irregularity was noted on the supraspinatus outlet radiograph of one shoulder. These differences between the os acromiale and control groups were significant (p < 0.0001). The overall sensitivities of the anteroposterior, axillary, and supraspinatus outlet views for the detection of an os acromiale were 82.4%, 94.1%, and 73.5%, respectively. The overall specificities of the three views were 95.2%, 100%, and 98.4%, respectively. The interobserver reliabilities of the three views were 0.66, 0.88, and 0.7, respectively (p < 0.0001). CONCLUSIONS: The double-density sign on a standard anteroposterior radiograph of the shoulder and a cortical irregularity on the supraspinatus outlet view are highly suggestive of an os acromiale. An os acromiale should be suspected in a patient with these radiographic findings. LEVEL OF EVIDENCE: Diagnostic study, Level IV-1 (case-control study). See Instructions to Authors for a complete description of levels of evidence.

The incidence of wrist interosseous ligament and triangular fibrocartilage articular disc disruptions: a cadaveric study.

PURPOSE: The purpose of this cadaveric wrist study was to determine the incidence and size of defects of the scapholunate interosseous ligament (SLIL), lunotriquetral interosseous ligament (LTIL), and triangular fibrocartilage (TFC) articular disc, and to determine their relationship to wrist arthrosis. METHODS: The status of the SLIL, LTIL, and the TFC articular disc was determined in 96 cadaveric wrists with an average age of 75 years (range, 61-92 y). The location and length of the SLIL and LTIL ligament disruptions and the site of ligament detachment were noted. Ligament disruptions were classified into 1 of 3 grades based on the size of the ligament disruption and the absence (grade 1 and 2 disruptions) or presence (grade 3 disruption) of wrist arthrosis. The location, size, and configuration of the TFC articular disc disruptions also were noted. RESULTS: Disruptions of the SLIL were noted in 34 wrists (35%). There were 20 grade 1, 4 grade 2, and 10 grade 3 ligament disruptions. The average length of ligament disruption was 10.9 mm, or 40% of the length of the ligament. Twenty-four of 34 SLIL disruptions occurred without wrist arthrosis. Disruptions of the LTIL were noted in 47 wrists (49%). There were 23 grade 1, 10 grade 2, and 14 grade 3 ligament disruptions. The average length of ligament disruption was 7.6 mm, or 52% of the ligament length. Thirty-three of 47 LTIL disruptions occurred without wrist arthrosis. Disruptions of the TFC articular disc were noted in 58 wrists (60%). The most common patterns of disruption were either a linear defect at the radial attachment of the articular disc or a centrally located oval defect. Thirty-seven of the 58 TFC articular disc disruptions were noted in wrists without distal radioulnar joint (DRUJ) arthrosis. CONCLUSIONS: There is a high incidence of SLIL, LTIL, and TFC articular disc disruptions in the cadaveric model. Large ligament and TFC articular disc disruptions without wrist arthrosis are very common.

Selective and long-lasting neural blockade with resiniferatoxin prevents inflammatory pain hypersensitivity.

UNLABELLED: Capsaicin can produce a selective and long-lasting neural blockade. Resiniferatoxin (RTX) is an ultrapotent vanilloid agonist with a unique spectrum of activities different from that of capsaicin. We sought to determine whether a single application of RTX to a peripheral nerve could completely prevent the long-lasting mechanical hyperalgesia caused by carrageenan injection. In rat experiments, RTX (0.001%) was administered percutaneously to the sciatic and saphenous nerves before the intraplantar injection of carrageenan. Responses to noxious mechanical (pressure on the paw) and thermal (hot plate) stimulations and changes in paw circumference were measured at various time intervals for 8 days after treatment. The administration of RTX resulted in mechanical and thermal hypoalgesia (for 2 and 8 days, respectively). Inflammatory hyperalgesia was completely prevented by the precarrageenan injection of RTX. Inflammatory enhancement of paw circumference was reduced by RTX (12.0 +/- 2.4 mm versus 6.9 +/- 3.4 mm, P < 0.005). We suggest that the selective nature of the effect of vanilloid agonists on nociception could provide an opportunity for prolonged neural blockade when early mobilization and/or preservation of protective sensation are required. IMPLICATIONS: We report that an ultrapotent vanilloid agonist resiniferatoxin can provide a selective and long-lasting neural blockade. Applied to the sciatic and saphenous nerves, it completely prevented pain hypersensitivity caused by prolonged inflammatory process (injection of carrageenan into the paw).

Simulation study of a panel of reliability indicators applied to paired measurements.

Reliability is a subject of continuing discussion in biomedial specialty areas, including physical anthropology and nutritional epidemiology. The purpose of this study was to explore techniques of detecting differences between two evaluators or methods. A field study in which anthropometric dimensions would be taken by two independent evaluators on each participant in a study group was simulated. A panel of reliability indicators was applied across a broad range of parameters using simulation, and then the panel was applied to field anthropometric data. The panel consisted of the intraclass correlation coefficient (ICC), paired t-test, a simultaneous test of evaluator means and variances, technical error of measurement, mean absolute difference, and mean difference. The simultaneous test for equal evaluator means and variances uses regression to model paired differences versus paired sums. The simulation demonstrated general properties of the reliability indicators across many conditions of population variance, measurer bias, and measurer error variance. High values of ICC often exist in cases in which the measurers are different. The simultaneous test is thus a powerful method for detecting measurer differences, especially when combined with the paired t-test. However, a single reliability indicator that is sufficient to determine all measurer inconsistencies was not identified. The field study and the simulation permitted the development of a logical approach to determining the source and magnitude of measurer differences using the panel of reliability indicators. © 1994 Wiley-Liss, Inc.

The effect of pre-incisional infiltration of tonsils with bupivacaine on the pain following tonsillectomy under general anesthesia.

The aim of the present study was to test the hypothesis that blockade of nociceptive input with bupivacaine during tonsillectomy can decrease pain beyond the immediate postoperative period. Fourteen patients between the ages of 6 and 18 years scheduled for tonsillectomy (with or without adenoidectomy) were randomly divided into two groups. The patients of both groups received 0.006 mg/kg atropine and anesthesia was induced by inhalation of halothane. Atracurium 0.5 mg/kg was used for myorelaxation. After oral intubation anesthesia was maintained with isoflurane plus nitrous oxide 67% in oxygen. In the bupivacaine group, 5 min before incision the tonsillar fossae were infiltrated with 0.25% bupivacaine with epinephrine (1 : 200,000). In the control group, the tonsillar fossae were infiltrated with normal saline with epinephrine (1 : 200,000). All patients received morphine 0.07 mg/kg (in the recovery room) and oral elixir with codeine 0.05 mg/kg plus acetaminophen 5 mg/kg every 4 h. Pain assessments were made using the visual analog (100 mm scale) self-rating method. Two types of pain were assessed: constant incisional pain and pain caused by drinking 100 ml of water. In the bupivacaine group, the constant pain score on the second day after surgery was 19 +/- 6 compared to 74 +/- 8 in the saline group (P less than 0.0002). By the 4-5th day after surgery almost no constant pain occurred in the bupivacaine group, but the pain score remained at the 40-60 level in the saline group. The difference in pain intensity on swallowing between the bupivacaine and saline groups was present even on the 10th postoperative day (1 +/- 1 vs. 14 +/- 5, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)