Pharmacology of Neuropathic Pain

Ollat, H; Césaro, P.

doi:10.1097/00002826-199510000-00002

Cited by 38 publications

(15 citation statements)

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“…In spite of the availability of opioids, reuptake inhibitors of noradrenaline and serotonin, and anticonvulsants, the treatment of neuropathic pains in patients, and of trigeminal neuralgia in particular, remains largely unsatisfactory (Ollat and Cesaro, 1995;Jensen, 1999, 2002;Attal, 2001). In a rat model of trigeminal neuropathic pain, in which a chronic constriction injury of the infraorbital nerve (IoN-CCI) causes von Frey hair stimulation of the skin area within the IoN territory to elicit allodynia-like behavior , it was shown that the GABA-B receptor agonist baclofen and the novel anticonvulsant gabapentin, but not the anticonvulsants carbamazepine or lamotrigine, morphine, or the tricylic antidepressants amitriptyline and clomipramine, partially attenuate the allodynia-like behavior (Idä npää n-Heikkilä and Guilbaud, 1999;Christensen et al, 2001).…”

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confidence: 99%

Continuous Administration of the 5-Hydroxytryptamine_1A Agonist (3-Chloro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl) -amino]-methyl}piperidin-1-yl]-methadone (F 13640) Attenuates Allodynia-Like Behavior in a Rat Model of Trigeminal Neuropathic Pain

Deseure¹,

Koek²,

Adriàensen³

et al. 2003

J Pharmacol Exp Ther

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ABSTRACT(3-Chloro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl)-amino]-methyl}piperidin-1-yl]-methadone (F 13640) is a recently discovered high-efficacy 5-hydroxytryptamine (HT) 1A receptor agonist that produces central analgesia through the neuroadaptive mechanisms of inverse tolerance and cooperation. In a rat model of trigeminal neuropathic pain, the chronic constriction injury of the infraorbital nerve causes allodynia-like behavior that develops within 2 weeks and remains stable thereafter. We report that early after surgery, during which time allodynia develops, the continuous 2-week infusion of 0.63 mg/day F 13640 inhibited the allodynia-like behavior, whereas 5 mg/day morphine showed no significant effect. When F 13640 infusion was initiated late after surgery, when allodynia was well established, it produced an antiallodynic effect that was apparent during the entire infusion period. In contrast, morphine infusion caused an initially marked antiallodynic effect to which tolerance developed within the 2-week infusion period. The GABA-B receptor agonist baclofen (1.06 mg/day) that has a recognized usefulness in the treatment of trigeminal neuralgia, demonstrated effectiveness in both conditions. The data are consistent with a theory of nociceptive signal transduction, as well as with previous data, in demonstrating the neuroadaptive mechanisms of inverse tolerance and cooperation. That is, in contrast with morphine, the antiallodynic effect induced by 5-HT 1A receptor activation does not decay, but, if anything, grows with chronicity. Also, 5-HT 1A receptor activation seemed to cooperate with nociceptive stimulation in, paradoxically, inducing an antiallodynic effect. The data presented here suggest that F 13640 may perhaps offer a lasting treatment of trigeminal neuralgia.The 5-HT 1A receptor agonist F 13640 has been shown to display a unique pattern of actions that is best understood in terms of a new theory of the mechanisms of pain and analgesia. This concept of signal transduction in nociceptive systems (Colpaert, 1978(Colpaert, , 1996Colpaert and Frégnac, 2001) specifies that any input to such systems causes not a single effect but two effects that are bidirectional, or opposite in sign. Thus, morphine produces both analgesia as a so-called first order effect, and also hyperalgesia as a second order effect. Upon chronic exposure to morphine, the second order hyperalgesia grows and neutralizes the first order analgesia (i.e., development of tolerance); the concept thus provides an account of the neuroadaptive actions that dynamically ensue upon -opioid receptor activation (Colpaert, 1996). Also, according to this concept, nociceptive stimulation should similarly produce dual, bidirectional effects that should amount to the mirror opposite of those produced by morphine.We have recently discovered ) that high-efficacy activation of 5-HT 1A receptors constitutes a molecular mechanism that mimics the central actions of nociceptive stimulation. A single injection of the selective, highef...

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confidence: 99%

Continuous Administration of the 5-Hydroxytryptamine_1A Agonist (3-Chloro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl) -amino]-methyl}piperidin-1-yl]-methadone (F 13640) Attenuates Allodynia-Like Behavior in a Rat Model of Trigeminal Neuropathic Pain

Deseure¹,

Koek²,

Adriàensen³

et al. 2003

J Pharmacol Exp Ther

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“…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.…”

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confidence: 99%

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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“…An increase in side effects may then lead to a decrease in analgesic dose resulting in the patient experiencing more pain. This creates a vicious circle of insufficient analgesia and side effects, both of which can lead to low patient compliance and treatment discontinuation [12][13][14] . These problems can lead to a reluctance to prescribe them, particularly for non-cancer pain 7,9,15 .…”

Section: I a L D I S T R I B U T I O N U N A U T H O R I Z E D U S mentioning

confidence: 99%

Opioids: a two-faced Janus

Ahlbeck

2011

Current Medical Research and Opinion

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Background: Long-term pain is a debilitating condition that is costly to treat and has a significant impact on patient quality of life. Classical opioids have been used for the treatment of pain for centuries and are one of the most effective drug classes available for acute severe pain and long-term pain. However, concerns regarding adverse effects, tolerance to analgesic effects and the potential for addiction have resulted in a reluctance to prescribe and use opioids for the management of long-term non-cancer pain. Adverse events, including gastrointestinal side effects such as constipation, nausea and vomiting, and central nervous system side effects such as sedation are responsible for as many as one in five patients discontinuing opioid treatment, often leading to inadequate pain relief and poor patient quality of life. Therefore, new analgesic therapies are needed that are associated with fewer adverse effects, whilst providing sustainable pain relief for patients with long-term pain.

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Pharmacology of Neuropathic Pain

Cited by 38 publications

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Continuous Administration of the 5-Hydroxytryptamine_1A Agonist (3-Chloro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl) -amino]-methyl}piperidin-1-yl]-methadone (F 13640) Attenuates Allodynia-Like Behavior in a Rat Model of Trigeminal Neuropathic Pain

Continuous Administration of the 5-Hydroxytryptamine_1A Agonist (3-Chloro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl) -amino]-methyl}piperidin-1-yl]-methadone (F 13640) Attenuates Allodynia-Like Behavior in a Rat Model of Trigeminal Neuropathic Pain

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

Opioids: a two-faced Janus

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Pharmacology of Neuropathic Pain

Cited by 38 publications

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Continuous Administration of the 5-Hydroxytryptamine1A Agonist (3-Chloro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl) -amino]-methyl}piperidin-1-yl]-methadone (F 13640) Attenuates Allodynia-Like Behavior in a Rat Model of Trigeminal Neuropathic Pain

Continuous Administration of the 5-Hydroxytryptamine1A Agonist (3-Chloro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl) -amino]-methyl}piperidin-1-yl]-methadone (F 13640) Attenuates Allodynia-Like Behavior in a Rat Model of Trigeminal Neuropathic Pain

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

Opioids: a two-faced Janus

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Continuous Administration of the 5-Hydroxytryptamine_1A Agonist (3-Chloro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl) -amino]-methyl}piperidin-1-yl]-methadone (F 13640) Attenuates Allodynia-Like Behavior in a Rat Model of Trigeminal Neuropathic Pain

Continuous Administration of the 5-Hydroxytryptamine_1A Agonist (3-Chloro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl) -amino]-methyl}piperidin-1-yl]-methadone (F 13640) Attenuates Allodynia-Like Behavior in a Rat Model of Trigeminal Neuropathic Pain