Biomedical subjects

T J Coderre

Publications and source records attributed to T J Coderre.

65 records · Page 4Linked to original sources

PubMed1988

Beta 2-adrenergic mechanisms in experimental arthritis.

We have studied (i) the contribution of specific adrenergic receptors to the proinflammatory effects of the sympathetic nervous system in experimental arthritis and (ii) the phases of the disease during which the sympathetic nervous system influences joint injury. Severity of joint injury was measured radiographically 28 days after induction of adjuvant arthritis in control rats and in rats treated with a variety of sympatholytic agents at various times during the course of the disease. Rats treated with a nonspecific catecholamine depletor (reserpine) or a beta-adrenergic receptor antagonist (propranolol) had a delayed onset and significantly less severe joint injury than saline-treated controls when treatment began prior to injection of the adjuvant and continued to day 28 after the injection. When administered over the same treatment period, neither nonselective (phenoxybenzamine) nor selective [prazosin (alpha 1) and yohimbine (alpha 2)] alpha-adrenergic receptor antagonists affected the onset or severity of joint injury. Metoprolol, a beta 1 antagonist, was also without effect. In contrast, two beta 2 antagonists (butoxamine and ICI 118,551) significantly retarded disease onset and reduced the severity of joint injury. When reserpine or butoxamine treatment was initiated after the onset of clinically apparent arthritis, it was still possible to favorably influence the course of the disease. These data indicate an important contribution of the beta 2-adrenergic receptor to joint injury in experimental arthritis.

Animals↗

PubMed1988

Potentiation of pentazocine analgesia by low-dose naloxone.

The analgesia produced by combinations of low-dose naloxone with pentazocine or morphine was studied in 105 patients with moderately severe postoperative pain after standardized surgery for removal of impacted third molars. Pain intensity was quantified using a visual-analogue scale. To eliminate the release of endogenous opioids produced by the placebo component of open drug administration, all injections were made by a preprogrammed infusion pump. The analgesia produced by pentazocine, an agonist-antagonist opiate-analgesic acting predominantly at the kappa opiate receptor, was potentiated by low-dose naloxone, whereas the analgesia produced by morphine, a mu-agonist, was attenuated by low-dose naloxone. To evaluate whether similar potentiation would be present in an animal model, and specifically, in the absence of diazepam, which patients receive, we performed an analogous experiment in rats in which nociceptive threshold was determined using the Randall-Selitto paw-withdrawal test. The results were completely analogous to the clinical results: pentazocine analgesia was potentiated by low-dose naloxone, whereas morphine analgesia was attenuated by low-dose naloxone. These data demonstrate a novel interaction between opiates, and suggest a rationale for opiate combinations to produce potent analgesia with fewer autonomic side effects and less abuse potential than presently available analgesics.

Analgesia↗

PubMed1987

Cutaneous hyperalgesia: contributions of the peripheral and central nervous systems to the increase in pain sensitivity after injury.

This study assesses the contributions of the peripheral and central nervous systems in the development of hyperalgesia (increased pain sensitivity) after an injury. Experiments were carried out to examine the role of C-fiber afferents, the spinal cord and sympathetic efferents on inflammation, primary hyperalgesia and referred hyperalgesia produced in rats by a heat injury. A peripheral mechanism was indicated since both primary hyperalgesia and inflammation after a heat injury were significantly attenuated by blocking C-fiber afferents with local capsaicin. In addition, a central mechanism was indicated since the spread of hyperalgesia to the paw contralateral to a heat injury was prevented by either spinal anesthesia or the blocking of sympathetic efferents by guanethidine. A further role for central mechanisms was indicated since referred hyperalgesia--the enhancement of self-mutilation (autotomy) of a denervated limb which had previously sustained a heat injury--was reduced by spinal anesthesia or a combined blocking of C-fiber afferents and sympathetic efferents with intrathecal capsaicin + guanethidine. The results strongly suggest that referred hyperalgesia after a heat injury is dependent on increased spinal cord activity. However, autotomy in rats that did not undergo a previous injury was unaffected by either spinal anesthesia or intrathecal capsaicin. This suggests that spinal cord hyperactivity, although it plays a role in hyperalgesia following a heat injury, is not a crucial factor in producing pain and hyperalgesia after a nerve injury.

Animals↗

PubMed1986

Autotomy after nerve sections in the rat is influenced by tonic descending inhibition from locus coeruleus.

This study examined the role of descending brainstem inhibition on autotomy (self-mutilation) produced by neurectomy, and on the enhancement of autotomy by an injury prior to denervation. Autotomy after sciatic and saphenous nerve sections was examined following lesions of the locus coeruleus (or sham lesions) in rats which were either uninjured or previously injured by an injection of formalin into the hindpaw. The prior injury of the paw produced a significant increase in autotomy which occurred earlier in rats with lesions of the locus coeruleus than in the sham controls. The locus coeruleus lesion by itself also produced an enhancement of autotomy. These results suggest that self-mutilation following neurectomy, and possibly its enhancement by prior injury, are subject to tonic inhibition due to descending controls from the locus coeruleus.

Animals↗

PubMed1986

Autotomy following sciatic and saphenous nerve sections: sparing of the medial toes after treatment of the sciatic nerve with capsaicin.

Autotomy, or self-mutilation of the foot following sciatic and saphenous nerve lesions, was examined in rats after pretreatment of the sciatic nerve with capsaicin. This pretreatment produced an alteration in autotomy behavior which resulted in the sparing of the medial side of the foot. The effect occurred following a long (12-week) pretreatment-test interval, but not after shorter (1- and 4-week) intervals. The effect also depended on the successive transecting of the saphenous and sciatic nerves. Sparing of the medial side of the foot occurred only when the saphenous nerve was transected at the time of the sciatic nerve treatment with capsaicin. Because the side of the foot innervated by the saphenous nerve was spared by treating the sciatic nerve with capsaicin, we suggest that capsaicin alters the course of autotomy by preventing collateral innervation of the saphenous region by the intact sciatic nerve during the pretreatment-test interval. The fact that this occurs only after a 12-week interval suggests that capsaicin's effect on collateral innervation is a gradual process that requires a long time to develop.

Animals↗

PubMed1986

Procedures which increase acute pain sensitivity also increase autotomy.

Rats typically display self-mutilation (autotomy) of a paw that has been denervated by transection of the sciatic and saphenous nerves. The cause of autotomy, however, is not known. It may be due to hyperesthesia (comparable to that seen in humans after peripheral nerve injury) or anesthesia (as an attempt to shed an insensate appendage). The present study tested the assumption that if autotomy is produced by pain, then procedures that normally augment the expression of pain should enhance autotomy after transection of peripheral nerves. Groups of rats were subjected to procedures known to produce an increase in pain sensitivity: (i) prior heat injury of either the ipsilateral or contralateral paw; (ii) systemic injection of noradrenaline and the monoamine oxidase inhibitor, pargyline; and (iii) intrathecal administration of substance P. The results showed that each of these procedures produced an increase in the level of autotomy. These results strongly suggest that autotomy is due to a sensory phenomenon which, in terms of human experience, would be described as pain or dysesthesia.

Animals↗

PubMed1985

Increased pain sensitivity following heat injury involves a central mechanism.

This study presents evidence for a central mechanism of hyperalgesia by showing that heat injury causes an increase in pain sensitivity even if the injured region is denervated shortly after injury. Increased pain sensitivity was demonstrated by increased autotomy following total nerve sections in an injured limb, and by reduced foot-withdrawal latencies in the paw contralateral to an injury.

Animals↗

PubMed1984

Behavioral evidence in rats for a peptidergic-noradrenergic interaction in cutaneous sensory and vascular function.

Cutaneous sensory and vascular function was examined following application of capsaicin to the sciatic nerve and systemic injection of guanethidine. Together the two drugs produced a reduction in sensitivity to heat-pain, inflammatory pain (formalin test), tactile stimulation and skin temperature of the foot that exceeded the effects of either drug alone. The inflammation produced by an injection of formalin to the plantar surface of the hind paw was reduced equally by capsaicin or capsaicin + guanethidine. Cold sensitivity and inflammation produced by yeast injection were unaffected by all treatments. The data imply a peripheral interaction between peptidergic and noradrenergic systems with significant functional implications that may be important in the pathology of familial dysautonomia.

Animals↗

PubMed1984

Stress analgesia: effects of PCPA, yohimbine, and naloxone.

Evidence suggests that morphine analgesia depends on the integrity of monoaminergic transmitter systems. Some forms of stress analgesia seem to be related to morphine analgesia, while others are not. To assess whether opioid and non-opioid stress analgesia differ in their reliance on monoamine systems, the effects of parachlorophenylalanine (PCPA) and yohimbine on analgesia produced by prolonged intermittent and brief continuous footshock were examined on the hotplate test. The interaction of adrenergic and endorphinergic activity with serotonergic mechanisms following these stressors was also investigated by testing the effects of yohimbine and naloxone on rats with prior PCPA treatment. Yohimbine alone significantly reduced baseline hotplate latencies, while PCPA and naloxone did not. The two stressors differed in the effects produced by both naloxone and PCPA. Naloxone significantly reversed stress analgesia in the prolonged stress condition, but not the brief stress condition. PCPA significantly enhanced the antinociceptive effect of brief continuous shock, while leaving the response to prolonged intermittent shock unaffected. In contrast, yohimbine blocked the analgesic effects of prolonged stress. For the brief stress condition, naloxone reversed the elevated thresholds elicited in PCPA treated rats. Naloxone also reversed stress analgesia for PCPA treated rats exposed to prolonged intermittent stress. Yohimbine lowered the responses of PCPA treated rats subjected to brief continuous shock. These results support an interactive model of stress analgesia dependent upon serotonergic, adrenergic, and endorphinergic transmitter systems.

Analgesia↗

PubMed1983

Naloxone hyperalgesia and stress-induced analgesia in rats.

Since past studies concerning the effects of naloxone on nociception have yielded inconclusive findings, the variables of pain test, baseline sensitivity, and stress condition were examined. Within a pure-bred strain of rats, consistent individual differences did not occur. All three measures of pain responsiveness demonstrated hyperalgesic effects of naloxone, but they differed in their capacity to reflect the effects of analgesia produced by continuous or intermittent electrical shock. By some measures, naloxone reversed the stress-induced analgesia due to intermittent shock; it did not influence the analgesia produced by continuous stress. The data support a model of pain inhibition involving both opioid and non-opioid systems and suggest that the hyperalgesic effects of naloxone can sometimes give rise to erroneous conclusions concerning apparent naloxone-reversability of putative analgesic procedures.

Analgesia↗

PubMedDate not supplied

The role of excitatory amino acid receptors and intracellular messengers in persistent nociception after tissue injury in rats.

Increased pain sensitivity (hyperalgesia) and persistent nociception following peripheral tissue injury depends both on an increase in the sensitivity of primary afferent nociceptors at the site of injury (peripheral sensitization), and on an increase in the excitability of neurons in the central nervous system (central sensitization). We will review evidence that central sensitization, and the persistent nociception it leads to, are dependent on an action of glutamate and aspartate at excitatory amino acid (EAA) receptors. Additional evidence will be presented implicating a role of various intracellular second messengers that are coupled to EAA receptors (nitric oxide, arachidonic acid, and protein kinase C) to central sensitization and persistent nociception following tissue injury. Finally, we will examine the evidence for a contribution of molecular events, including noxious stimulus-induced expression of immediate-early genes such as c-fos to persistent nociception.

Afferent Pathways↗