Gabapentin suppresses ectopic nerve discharges and reverses allodynia in neuropathic rats.
Repetitive ectopic discharges from injured afferent nerves play an important role in initiation and maintenance of neuropathic pain. Gabapentin is effective for treatment of neuropathic pain but the sites and mechanisms of its antinociceptive actions remain uncertain. In the present study, we tested a hypothesis that therapeutic doses of gabapentin suppress ectopic afferent discharge activity generated from injured peripheral nerves. Mechanical allodynia, induced by partial ligation of the sciatic nerve in rats, was determined by application of von Frey filaments to the hindpaw. Single-unit afferent nerve activity was recorded proximal to the ligated sciatic nerve site. Intravenous gabapentin, in a range of 30 to 90 mg/kg, significantly attenuated allodynia in nerve-injured rats. Furthermore, gabapentin, in the same therapeutic dose range, dose-dependently inhibited the ectopic discharge activity of 15 injured sciatic afferent nerve fibers through an action on impulse generation. However, the conduction velocity and responses of 12 normal afferent fibers to mechanical stimulation were not affected by gabapentin. Therefore, this study provides electrophysiological evidence that gabapentin is capable of suppressing the ectopic discharge activity from injured peripheral nerves. This action may contribute, at least in part, to the antiallodynic effect of gabapentin on neuropathic pain. (+info)
The novel analgesic compound OT-7100 (5-n-butyl-7-(3,4,5-trimethoxybenzoylamino)pyrazolo[1,5-a]pyrimid ine) attenuates mechanical nociceptive responses in animal models of acute and peripheral neuropathic hyperalgesia.
We investigated the effects of OT-7100, a novel analgesic compound (5-n-butyl-7-(3,4,5-trimethoxybenzoylamino)pyrazolo[1,5-a]pyrimidi ne), on prostaglandin E2 biosynthesis in vitro, acute hyperalgesia induced by yeast and substance P in rats and hyperalgesia in rats with a chronic constriction injury to the sciatic nerve (Bennett model), which is a model for peripheral neuropathic pain. OT-7100 did not inhibit prostaglandin E2 biosynthesis at 10(-8)-10(-4) M. Single oral doses of 3 and 10 mg/kg OT-7100 were effective on the hyperalgesia induced by yeast. Single oral doses of 0.1, 0.3, 1 and 3 mg/kg OT-7100 were effective on the hyperalgesia induced by substance P in which indomethacin had no effect. Repeated oral administration of OT-7100 (10 and 30 mg/kg) was effective in normalizing the mechanical nociceptive threshold in the injured paw without affecting the nociceptive threshold in the uninjured paw in the Bennett model. Indomethacin had no effect in this model. While amitriptyline (10 and 30 mg/kg) and clonazepam (3 and 10 mg/kg) significantly normalized the nociceptive threshold in the injured paw, they also increased the nociceptive threshold in the uninjured paw. These results suggest that OT-7100 is a new type of analgesic with the effect of normalizing the nociceptive threshold in peripheral neuropathic hyperalgesia. (+info)
Nerve injury associated with anesthesia: a closed claims analysis.
BACKGROUND: Nerve injury associated with anesthesia is a significant source of morbidity for patients and liability for anesthesiologists. To identify recurrent and emerging patterns of injury we analyzed the current American Society of Anesthesiologists (ASA) Closed Claims Project Database and performed an in-depth analysis of claims for nerve injury that were entered into the database since the authors' initial report of the subject. METHODS: The ASA Closed Claims Database is a standardized collection of case summaries derived from the closed claims files of professional liability insurance companies. Claims for nerve injury that were not included in the authors' 1990 report were reviewed in-depth. RESULTS: Six hundred seventy (16% of 4,183) claims were for anesthesia-related nerve injury. The most frequent sites of injury were the ulnar nerve (28%), brachial plexus (20%), lumbosacral nerve root (16%), and spinal cord (13%). Ulnar nerve (85%) injuries were more likely to have occurred in association with general anesthesia, whereas spinal cord (58%) and lumbosacral nerve root (92%) injuries were more likely to occur with regional techniques. Ulnar nerve injury occurred predominately in men (75%) and was also more apt to have a delayed onset of symptoms (62%) than other nerve injuries. Spinal cord injuries were the leading cause of claims for nerve injury that occurred in the 1990s. CONCLUSION: New strategies for prevention of nerve damage cannot be recommended at this time because the mechanism for most injuries, particularly those of the ulnar nerve, is not apparent. (+info)
Incidence and importance of lower extremity nerve lesions after infrainguinal vascular surgical interventions.
OBJECTIVES: To determine the incidence of peripheral nerve lesions after arterial vascular surgery of the lower extremity. MATERIALS AND METHODS: 436 patients who underwent peripheral vascular surgery from January 1992 until December 1996 underwent a detailed postoperative neurological examination. RESULTS: 147 patients underwent profundaplasty, 140 above-knee femoropopliteal bypasses, 106 below-knee femoropopliteal bypasses and 56 femorotibial bypasses. There were 182 women and 254 men. Peripheral nerve lesions were observed in 11 patients (4%) after primary operations. 166 patients underwent reoperations (38%) and 55 of these developed nerve lesions (33%). CONCLUSIONS: Reoperation carries an 8-fold increased risk of nerve lesions compared with patients undergoing primary surgery. Detailed explanation of the risk of peripheral nerve lesions before vascular surgery of the lower limb is advisable. (+info)
Knee pain and the infrapatellar branch of the saphenous nerve.
Pain over the front of the knee is common after surgery or trauma but often a definite diagnosis is difficult to make. Over the past year we have seen five cases in which the pain could be ascribed to damage to a branch of the infrapatellar branch of the saphenous nerve. Two were subsequent to trauma and three to surgical procedures. In all five cases surgical exploration gave symptomatic relief. Eight cadaveric knees were prosected to explore further the anatomy of this nerve in relation to the injuries. Injury to one of these branches should be considered in cases of persistent anterior, anteromedial or anterolateral knee pain or neurological symptoms following surgery or trauma. (+info)
A comparison of the potential role of the tetrodotoxin-insensitive sodium channels, PN3/SNS and NaN/SNS2, in rat models of chronic pain.
Alterations in sodium channel expression and function have been suggested as a key molecular event underlying the abnormal processing of pain after peripheral nerve or tissue injury. Although the relative contribution of individual sodium channel subtypes to this process is unclear, the biophysical properties of the tetrodotoxin-resistant current, mediated, at least in part, by the sodium channel PN3 (SNS), suggests that it may play a specialized, pathophysiological role in the sustained, repetitive firing of the peripheral neuron after injury. Moreover, this hypothesis is supported by evidence demonstrating that selective "knock-down" of PN3 protein in the dorsal root ganglion with specific antisense oligodeoxynucleotides prevents hyperalgesia and allodynia caused by either chronic nerve or tissue injury. In contrast, knock-down of NaN/SNS2 protein, a sodium channel that may be a second possible candidate for the tetrodotoxin-resistant current, appears to have no effect on nerve injury-induced behavioral responses. These data suggest that relief from chronic inflammatory or neuropathic pain might be achieved by selective blockade or inhibition of PN3 expression. In light of the restricted distribution of PN3 to sensory neurons, such an approach might offer effective pain relief without a significant side-effect liability. (+info)
The incidence of nerve injury in anterior dislocation of the shoulder and its influence on functional recovery. A prospective clinical and EMG study.
Opinion varies as to the incidence of nerve lesions in anterior dislocation of the shoulder after low-velocity trauma. Most studies are retrospective or do not use EMG. We have investigated the incidence and the clinical consequences of nerve lesions in a prospective study by clinical and electrophysiological examination. Axonal loss was seen in 48% of 77 patients. The axillary nerve was most frequently involved (42%). Although recovery as judged by EMG and muscle strength was almost complete, function of the shoulder was significantly impaired in patients with lesions of the axillary and suprascapular nerves. Unfavourable prognostic factors are increasing age and the presence of a haematoma. It is not necessary to carry out EMG routinely; an adequate programme of physiotherapy is important. In patients with a severe paresis, EMG is essential after three weeks. (+info)
Safety of the limited open technique of bone-transfixing threaded-pin placement for external fixation of distal radial fractures: a cadaver study.
OBJECTIVE: To examine the safety of threaded-pin placement for fixation of distal radial fractures using a limited open approach. DESIGN: A cadaver study. METHODS: Four-millimetre Schanz threaded pins were inserted into the radius and 3-mm screw pins into the second metacarpal of 20 cadaver arms. Each threaded pin was inserted in the dorsoradial oblique plane through a limited open, 5- to 10-mm longitudinal incision. Open exploration of the threaded-pin sites was then carried out. OUTCOME MEASURES: Injury to nerves, muscles and tendons and the proximity of these structures to the threaded pins. RESULTS: There were no injuries to the extensor tendons, superficial radial or lateral antebrachial nerves of the forearm, or to the soft tissues overlying the metacarpal. The lateral antebrachial nerve was the closest nerve to the radial pins and a branch of the superficial radial nerve was closest to the metacarpal pins. The superficial radial nerve was not close to the radial pins. CONCLUSION: Limited open threaded-pin fixation of distal radial fractures in the dorsolateral plane appears to be safe. (+info)