A comparison of intrathecally administered narcotic and nonnarcotic analgesics for experimental chronic neuropathic pain

Leiphart, James W.; Dills, Cynthia; Zikel, Ofer M.; Kim, Daniel L.; Levy, Robert M.

doi:10.3171/jns.1995.82.4.0595

Cited by 44 publications

(21 citation statements)

References 14 publications

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“…From a clinical point of view, this is promising because, in this study, the effects of melanocortins appear to be specific for the allodynia associated with a neuropathic pain state, without altering normal pain sensation by inducing a more general analgesia. This specificity for the hyperalgesia underlying neuropathic pain without affecting baseline pain detection has also been reported for the ␣2-adrenergic agonist tizanidine (Leiphart et al, 1995).…”

Section: Discussionmentioning

confidence: 85%

Antagonism of the Melanocortin System Reduces Cold and Mechanical Allodynia in Mononeuropathic Rats

Vrinten

Gispen²,

Groen

et al. 2000

J. Neurosci.

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The presence of both pro-opiomelanocortin-derived peptides and melanocortin (MC) receptors in nociception-associated areas in the spinal cord suggests that, at the spinal level, the MC system might be involved in nociceptive transmission. In the present study, we demonstrate that a chronic constriction injury (CCI) to the rat sciatic nerve, a lesion that produces neuropathic pain, results in changes in the spinal cord MC system, as shown by an increased binding of 125 I-NDP-MSH to the dorsal horn. Furthermore, we investigated whether intrathecal administration (in the cisterna magna) of selective MC receptor ligands can affect the mechanical and cold allodynia associated with the CCI. Mechanical and cold allodynia were assessed by measuring withdrawal responses of the affected limb to von Frey filaments and withdrawal latencies upon immersion in a 4.5°C water bath, respectively. We show that treatment with the MC receptor antagonist SHU9119 has a profound anti-allodynic effect, suggesting that the endogenous MC system has a tonic effect on nociception. In contrast, administration of the MC4 receptor agonists MTII and D-Tyr-MTII primarily increases the sensitivity to mechanical and cold stimulation. No antinociceptive action was observed after administration of the selective MC3 receptor agonist Nle-␥-MSH. Together, our data suggest that the spinal cord MC system is involved in neuropathic pain and that the effects of MC receptor ligands on the responses to painful stimuli are exerted through the MC4 receptor. In conclusion, antagonism of the spinal melanocortin system might provide a new approach in the treatment of neuropathic pain. Key words: neuropathic pain; chronic constriction injury; allodynia; melanocortins; melanocortin-4 receptor; spinal cord; dorsal horn; in situ 125 I-NDP-MSH bindingIn humans, damage to the nervous system (a peripheral nerve, dorsal root ganglion, dorsal root, or the CNS) can lead to a pain state referred to as neuropathic pain. This syndrome is characterized by spontaneous pain in combination with allodynia (pain evoked by normally nonpainful stimuli) and hyperalgesia (an increased response to painful stimuli). In current clinical practice, several drugs are used to control neuropathic pain, including tricyclic antidepressants (for review, see Ollat and Cesaro, 1995;Kingery, 1997), anticonvulsants (Rosenberg et al., 1997), systemic administration of local anesthetics (Glazer and Portenoy, 1991;Rowbotham et al., 1991), and NMDA receptor antagonists (Backonja et al., 1994;Felsby et al., 1996). Despite this wide range of drugs, the treatment of neuropathic pain is often unsatisfactory and limited by the occurrence of adverse side effects. Over the past decade, a number of animal models of neuropathic pain have become available, producing symptoms that closely resemble those observed in human neuropathic pain. Research using these preclinical models has yielded an array of potential new analgesics, including different enzyme inhibitors, ion channel blockers, and ligands for various rece...

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Section: Discussionmentioning

confidence: 85%

Antagonism of the Melanocortin System Reduces Cold and Mechanical Allodynia in Mononeuropathic Rats

Vrinten

Gispen²,

Groen

et al. 2000

J. Neurosci.

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“…The diminished availability of functionally active spinal opioid receptors following nerve injury could be instrumental to the reduced effectiveness of intrathecally administered opioids [21,22]. Nerve ligation experiments conducted in the rat give rise to the assumption that intraperitoneally and intraventricularly applied morphine leads to a reduction of tactile allodynia much more via supraspinal than via spinal Ì-opioid receptors [23].…”

Section: Discussionmentioning

confidence: 99%

The Significance of Intrathecal Opioid Therapy for the Treatment of Neuropathic Cancer Pain Conditions

Becker

Jakob

Uhle

et al. 2000

Stereotact Funct Neurosurg

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The effectiveness of intrathecal opioid therapy when applied to different pain mechanisms, in particular neuropathic and nociceptive pain conditions, was studied retrospectively in 43 patients suffering from cancer pain. On the basis of clinical and radiological data, the pain mechanisms were categorized as nociceptive (n = 23) and neuropathic (n = 20). The average duration of treatment of nociceptive pain was 5 months, of neuropathic pain only 2.5 months. The initial median reduction of pain with intrathecal opioid therapy was 77.8% for nociceptive and 61.1% for neuropathic pain. Long-term results with patients suffering nociceptive pain showed a continuing good median pain reduction of 66.7%. Patients suffering from neuropathic pain showed poor long-term results (11.1% median pain reduction). Neuropathic pain in the extremities reacted least to the application of intrathecal opioids. Optimal results were obtained for nociceptive pain in the trunk area of the body.

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“…Alpha-2 adrenoceptor agonists have been reported to be useful adjuncts in the treatment of chronic pain syndromes in animal and human studies [175][176][177]. Lee & Yaksh [178] demonstrated that the intrathecal administration clonidine or MK-801, an N-methyl-D-aspartate antagonist (NMDA), abolished, in a dose-dependent manner, a model of neuropathic pain in rats.…”

Section: Chronic Painmentioning

confidence: 99%

Alpha‐2 and imidazoline receptor agonistsTheir pharmacology and therapeutic role

Khan¹,

Ferguson²,

Jones³

1999

Anaesthesia

605

423

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SummaryClonidine has proved to be a clinically useful adjunct in clinical anaesthetic practice as well as in chronic pain therapy because it has both anaesthetic and analgesic-sparing activity. The more selective alpha-2 adrenoceptor agonists, dexmedetomidine and mivazerol, may also have a role in providing haemodynamic stability in patients who are at risk of peri-operative ischaemia. The side-effects of hypotension and bradycardia have limited the routine use of alpha-2 adrenoceptor agonists. Investigations into the molecular pharmacology of alpha-2 adrenoceptors have elucidated their role in the control of wakefulness, blood pressure and antinociception. We discuss the pharmacology of alpha-2 adrenoceptors and their therapeutic role in this review.

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A comparison of intrathecally administered narcotic and nonnarcotic analgesics for experimental chronic neuropathic pain

Cited by 44 publications

References 14 publications

Antagonism of the Melanocortin System Reduces Cold and Mechanical Allodynia in Mononeuropathic Rats

Antagonism of the Melanocortin System Reduces Cold and Mechanical Allodynia in Mononeuropathic Rats

The Significance of Intrathecal Opioid Therapy for the Treatment of Neuropathic Cancer Pain Conditions

Alpha‐2 and imidazoline receptor agonistsTheir pharmacology and therapeutic role

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