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PubMed1986

Absence of ongoing activity in fibres arising from proximal nerve ends regenerating into mesothelial chambers.

Morphological studies have indicated that proximal nerve ends of transected rat sciatic nerves regenerating into preformed mesothelial chambers show a different organization as compared to neuromas developed in contact with a muscle fascia. We have studied the physiological properties of nerve fibres arising from these types of preparations with reference to ongoing activity, response to mechanical stimulation and noradrenaline sensitivity. The study included also fibres arising from ligated and encapsulated neuromas. Fibres with ongoing activity arising from the neuroma could be found from neuromas in contact with a muscle fascia and also from ligated and encapsulated neuromas. This ongoing activity was enhanced by mechanical stimulation and i.v. infusion of noradrenaline. In contrast, fibres arising from proximal nerve ends in mesothelial chambers did not show ongoing activity. These silent fibres responded dynamically to light mechanical stimulation. Noradrenaline did not induce ongoing activity in these fibres.

Animals↗
PubMed1987

Autotomy in rats after nerve section compared with nerve degeneration following intraneural injection of Ricinus communis agglutinin I.

Partial unilateral deafferentation of the hind limb of rats was carried out by section of the sciatic nerve or the intraneural injection of Ricinus communis agglutinin 1 (RCA I). The development of autotomy was observed over a 6 week period. The axotomized animals autotomized more than those injected with RCA I. A neuroma developed on the proximal stump of the axotomized nerves. Within 7 days the axons of the RCA I-injected nerve degenerated and the cell bodies in dorsal root ganglia L4 and L5 were destroyed. Since the RCA I-injected animals autotomized, it is concluded that purely central factors have a role in the generation of this abnormal behavior. As the axotomized animals autotomized more than the RCA I-treated ones it is further concluded that abnormal impulse activity arising from a neuroma may be an additional factor in causing autotomy.

Afferent Pathways↗
PubMed1990

Autotomy.

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Brachial Plexus↗
PubMed1990

Heritability of symptoms in an experimental model of neuropathic pain.

Male and female rats underwent transection and ligation of the sciatic and saphenous nerves, and the development of autonomy was monitored. The deafferented animals were then interbred, always selecting males and females that expressed relatively high and, alternatively, relatively low levels of autotomy. Offspring were similarly operated and interbred. By the sixth generation of selective breeding, lines were achieved in which autotomy was consistently high (HA) or consistently low (LA). There was no indication of sex linkage. Thermal and mechanical nocifensive responsiveness co-selected with propensity to express autotomy following nerve injury: response thresholds were lower in HA than in LA rats. F1 hybrids formed by crossing homozygous HA and LA animals showed low levels of autotomy, similar to LA stock. This indicates recessive inheritance of the autotomy trait. Backcrossing F1 hybrids onto the LA line yielded a low autotomy phenotype in almost all cases; backcrossing F1 hybrids onto HA stock yielded about 50% high autotomy and 50% low autotomy. These ratios are consistent with simple mendelian inheritance of a single gene. Taken together, the data suggest that autotomy is inherited as a single-gene autosomal recessive trait.

Afferent Pathways↗
PubMed1990

Interactions between substance P, calcitonin gene-related peptide, taurine and excitatory amino acids in the spinal cord.

Using in vivo microdialysis in the dorsal spinal cord of the rat, we have previously observed increases in glutamate and aspartate during exposure to a noxious stimulus. The present investigation was designed to determine whether these increases may be mediated by substance P. Infusion of 1 mM of substance P in the dialysis fluid increased the concentrations of glutamate and aspartate, similar to the response seen during noxious stimulation. In addition, substance P also increased the concentrations of the inhibitory amino acids glycine and taurine. Calcitonin gene-related peptide, previously shown to enhance substance P-induced biting and scratching behavior, produced no effect on amino acid release by itself but potentiated the apparent release of taurine by substance P. To assess the importance of substance P-induced amino acid release in sensory processing, we examined the influence of taurine and of excitatory amino acid antagonists on the biting and scratching behavior produced by excitatory amino acids and substance P. Taurine selectively inhibited only substance P-induced biting and scratching while excitatory amino acid antagonists inhibited only excitatory amino acid-induced behavior. To further explore the ability of taurine to inhibit the substance P-induced behavior, 3 tests of nociception were then used. Pretreatment with taurine inhibited the nociceptive-related writhing behavior produced by an intraperitoneal injection of acetic acid in mice but failed to alter the latency of response in the hot plate or tail flick assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The effects of oral morphine and buprenorphine on autotomy following brachial nerve sections in rat.

This study assessed the relationship between autotomy and opioid systems following brachial nerve sections in the rat. Morphine, buprenorphine and/or naloxone were self-administered orally to rats following nerve sections. Oral morphine and buprenorphine increased the severity of autotomy. Naloxone alone had no effect, but reversed oral morphine effect on autotomy. These results suggest that mu-receptor activation by morphine and buprenorphine can increase the severity of autotomy.

Administration, Oral↗
PubMed1992

The effects of streptomycin on autotomy.

Thirty-six rats with sciatic nerve transections and autotomy scores 1-2 were divided into 3 groups. Two groups were re-operated and injected with streptomycin sulphate or saline into the polyethylene tube around the neuroma. In the third group, streptomycin was injected at the sciatic nerve, extraneurally, proximal to the tube. Streptomycin injected into the polyethylene tube suppressed autotomy scores during the entire postinjection period. At the eighth postinjection week, none of the rats from this group reached the maximal autotomy score.

Animals↗
PubMed1992

Chronic pain-related syndrome in rats after ischemic spinal cord lesion: a possible animal model for pain in patients with spinal cord injury.

We examined a pain-related syndrome, which includes mechanical allodynia and autotomy, in rats after ischemic spinal cord injury photochemically induced by laser irradiation for 5-20 min. This procedure results in an acute allodynia-like phenomenon which lasts for several days and is possibly related to dysfunction of the GABAB system in the spinal cord. In some animals this is followed by a chronic allodynia-like symptom with an onset varying between 1 week and 1.5 months after injury, expressed as a clearly painful reaction to light pressure applied to a skin area at or near the dermatome of the injured spinal segments. In the majority of rats the allodynia persists over several months, in some cases accompanied by autotomy of the hind paws. Pharmacological studies indicated that the allodynia in the majority of rats could be relieved by systemic tocainide (75 mg/kg). Morphine was only effective at a sedative dose (5 mg/kg). The allodynia was not relieved by baclofen, muscimol, clonidine or carbamazepine. Low-dose systemic pentobarbital (5 mg/kg) had a slight beneficial effect. Guanethidine (20 mg/kg, s.c.) did not abolish the allodynia in most of the rats. Histological examination revealed massive damage in the spinal cord. The dorsal roots of the irradiated segments were also injured. No morphological abnormalities were seen in the dorsal root ganglia. The mechanism that may account for this chronic pain-related syndrome in spinally injured rats probably involves abnormalities in the central nervous system. The allodynia seen in chronic spinally injured rats was similar to some painful symptoms in patients after spinal cord injury or stroke. It is suggested that the chronic allodynia-like phenomenon may represent an animal model for studying the mechanisms of chronic central pain.

Animals↗
PubMed1994

Differential behavioral outcomes in the sciatic cryoneurolysis model of neuropathic pain in rats.

We have previously introduced a novel animal model of neuropathic pain in rats following a peripheral mononeuropathy produced by freezing the common sciatic nerve, a technique termed sciatic cryoneurolysis (SCN). In this study, we have further characterized the temporal pattern of behavioral changes following SCN, including thermal hyperalgesia and mechanical allodynia. These behaviors were assessed using noxious thermal (radiant heat) and non-noxious tactile (von Frey filament) stimuli, respectively. Following unilateral SCN, animals exhibited significant (P < 0.001) bilateral tactile hypersensitivity (allodynia) that persisted at least 10 weeks. However, this lesion did not result in thermal hypersensitivity (hyperalgesia). In fact, thermal sensitivity in the operated limb remained significantly suppressed throughout the 10 weeks (P < 0.001). Furthermore, we observed autotomy in 76% of SCN-lesioned animals as well as transient weight loss and pale eye syndrome (PES), a phenomenon previously unreported in other neuropathic pain models. PES is a sustained, visibly distinct pallor of the normally pink eye color of the albino rat. We believe PES is a putative marker of heightened sympathetic efferent activity. The severity of autotomy following SCN correlated significantly with both weight loss (P < 0.001) and the expression of PES (P < 0.001). Autotomy behavior preceded the onset of allodynia; however, there was no correlation between the severity of expression of these behaviors. These behavioral sequelae are comparable to those seen in other animal models of neuropathic pain, but differ in respect to the increased frequency of autotomy and the lack of thermal hyperalgesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The resolution of neuropathic hyperalgesia following motor and sensory functional recovery in sciatic axonotmetic mononeuropathies.

Nerve lesions producing extensive axonal loss can induce painful hyperalgesic states in man. The affect of axonal regeneration and end-organ reinnervation on hyperalgesia and pain is controversial. This study used two axonotmetic models, the sciatic crush injury (CI) and the sciatic chronic constrictive injury (CCI), to investigate the affects of nerve regeneration and reinnervation on hyperalgesia and presumed painful behavior in rats. The sciatic CI resulted in a transient loss of both sciatic motor function and the withdrawal response to pinch and heat in the sciatic distribution. Extensive recovery of motor function, pinch and heat response occurred over days 23-38 post-crush injury. This temporally corresponded with a plateau in the hindpaw autotomy score and a resolution of the saphenous-mediated pressure and heat hyperalgesia (adjacent neuropathic hyperalgesia; ANH) which developed over the medial dorsum of the hindpaw following the sciatic CI. In contrast, with sciatic transection and distal stump excision, no motor recovery occurs, large areas of the hindpaw remain unresponsive to heat and pinch, and the saphenous mediated ANH fails to resolve over a period of 3 months. When sciatic CI was compared to contralateral sciatic transection within the same rat, the bilateral saphenous-mediated pressure and heat thresholds were initially identical, but by 23-27 days post-crush, the crush side thresholds became hypoalgesic relative to the section side. This demonstrates an attenuation of the crush-induced ANH which temporally corresponds to the recovery of motor and sensory function. When the sciatic nerve was proximally crushed and distally transected (3 cm below the crush site), the saphenous-mediated pressure and heat threshold changes were identical (over 6 weeks of serial testing) to those produced by a contralateral sciatic transection within the same rat. This indicates that the microenvironments surrounding the regenerating axon tips did not differentially affect the development of ANH following sciatic CI or transection. The sciatic CCI resulted in a transient loss of hindpaw motor function without the loss of pinch or heat withdrawal responses in the sciatic distribution. Motor function recovery occurred primarily over days 23-59 post-ligature. During this prolonged period of motor function recovery there was a resolution of the sciatic-mediated plantar surface heat hyperalgesia and the saphenous-mediated heat ANH. The above data support the hypothesis that the successful regeneration of distal axons after axonotmetic lesions can initiate the resolution of neuropathic hyperalgesia.

Animals↗
PubMed1995

Effects of intrathecal local anesthetics on spinal excitability and on the development of autotomy.

The effect of 500 micrograms intrathecal (i.t.) lidocaine and tocainide injected prior to unilateral sciatic nerve section on the development of autotomy behavior was examined in rats. Neither drug inhibited autotomy compared with saline controls. The effect of lidocaine and tocainide on the flexor reflex in decerebrate, spinalized rats was also examined. Both drugs at 500 micrograms i.t. totally blocked the flexor reflex and hyperexcitability following acute nerve section, with a longer duration of action with tocainide. Recovery from the drugs was followed by a prolonged period of reflex hyperexcitability, even without axotomy. Lower dose lidocaine (100 micrograms) briefly blocked the reflex and recovery was followed by reflex hyperexcitability. Very low dose i.t. lidocaine (1 and 10 micrograms) did not block the flexor reflex, but only induced a prolonged increase in reflex magnitude. The possible mechanisms underlying these observations are discussed. The results suggest that i.t. local anesthetic pretreatment alone may not be beneficial for the prevention of the development of postoperative or neuropathic pain.

Anesthetics, Local↗
PubMed1984

Behavioural factors in burn mortality and length of stay in hospital.

Numerous studies have examined the effects of burn size and depth, age, concomitant injury, and illness upon burn patient mortality and duration of stay in hospital, and other studies have stressed the importance of psychosocial factors in the causation of burns. However, scant attention has been given to the effects of psychosocial factors on burn mortality and length of stay in hospital. Data on psychiatric diagnoses, substance abuse, and factors in severity of injury were abstracted from the charts of patients admitted to the San Diego Regional Burn Treatment Center. Mortality data were analysed using logistic regression. After adjusting for severity of the burn injury, statistically significant increases in mortality are associated with the diagnosis of character or personality disorder, schizophrenia, alcohol intoxication at the time of injury, and a variable indication a psychiatric diagnosis or severe undiagnosed problems. Comments on individual charts suggest that overtly self-destructive behaviour during treatment caused the increased mortality. Data on duration of stay in hospital among survivors were analysed using multiple linear regression. After adjusting for severity of injury, significantly longer stays are associated with suicidal intention, diagnosis of character or personality disorder, schizophrenia, senility and a variable indicating a psychiatric diagnosis or severe undiagnosed problems. Overtly self-destructive behaviour, treatment of psychiatric problems, and the inability of some patients to care for themselves may each contribute to the longer stay in hospital.

Adult↗
PubMed1985

Self-inflicted burns: a 5-year retrospective study.

Forty-two patients who had attempted suicide by burning were admitted to the North West Thames Regional Burns Unit over a 5-year period. Over three-quarters of these patients had previous psychiatric illness and a quarter had previously attempted suicide. In no case was political or religious protest a motive. The number of non-Caucasians was higher than expected from population statistics and fatal burns were more common in this group. The mean age was 36 years and the overall mortality rate was 48 per cent. The mortality was not significantly higher than for accidental burns of comparable severity.

Adult↗