Predictive validity of pharmacologic interventions in animal models of neuropathic pain

Per Gustaf Hartvig Honoré; Anna Basnet; Pernille Kristensen; Lene Munkholm Andersen; Signe Neustrup; Pia Møllgaard; Laila Eljaja; Ole Jannik Bjerrum

doi:10.1016/j.sjpain.2011.06.002

Predictive validity of pharmacologic interventions in animal models of neuropathic pain

Per Gustaf Hartvig Honoré, Anna Basnet, Pernille Kristensen, Lene Munkholm Andersen, Signe Neustrup, Pia Møllgaard, Laila Eljaja, Ole Jannik Bjerrum

5 Citations (Scopus)

Abstract

Introduction: The pathophysiologic and neurochemical characteristics of neuropathic pain must be considered in the search for new treatment targets. Breakthroughs in the understanding of the structural and biochemical changes in neuropathy have opened up possibilities to explore new treatment paradigms. However, long term sequels from the damage are still difficult to treat. Aim of the study: To examine the validity of pharmacological treatments in humans and animals for neuropathic pain. Method: An overview from the literature and own experiences of pharmacological treatments employed to interfere in pain behavior in different animal models was performed. Results: The treatment principles tested in animal models of neuropathic pain may have predictive validity for treatment of human neuropathies. Opioids, neurotransmitter blockers, drugs interfering with the prostaglandin syntheses as well as voltage gated sodium channel blockers and calcium channel blockers are treatment principles having efficacy and similar potency in humans and in animals. Alternative targets have been identified and have shown promising results in the validated animal models. Modulators of the glutamate system with an increased expression of glutamate re-uptake transporters, inhibition of pain promoters as nitric oxide and prostaglandins need further exploration. Modulation of cytokines and neurotrophins in neuropathic pain implies new targets for study. Further, a combination of different analgesic treatments may as well improve management of neuropathic pain, changing the benefit/risk ratio. Implications: Not surprisingly most pharmacologic principles that are tested in animal models of neuropathic pain are also found to be active in humans. Whereas many candidate drugs that were promising in animal models of neuropathic pain turned out not to be effective or too toxic in humans, animal models for neuropathic pain are still the best tools available to learn more about mechanisms of neuropathic pain. Better understanding of pathogenesis is the most hopeful approach to improve treatment of neuropathic pain.

Original language	Danish
Journal	Scandinavian Journal of Pain
Volume	2
Issue number	4
Pages (from-to)	178-184
Number of pages	6
DOIs	https://doi.org/10.1016/j.sjpain.2011.06.002
Publication status	Published - Oct 2011

Keywords

Former Faculty of Pharmaceutical Sciences

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10.1016/j.sjpain.2011.06.002

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@article{c38c38b418734979a1dab2ddd5662f51,

title = "Predictive validity of pharmacologic interventions in animal models of neuropathic pain",

abstract = "Introduction: The pathophysiologic and neurochemical characteristics of neuropathic pain must be considered in the search for new treatment targets. Breakthroughs in the understanding of the structural and biochemical changes in neuropathy have opened up possibilities to explore new treatment paradigms. However, long term sequels from the damage are still difficult to treat. Aim of the study: To examine the validity of pharmacological treatments in humans and animals for neuropathic pain. Method: An overview from the literature and own experiences of pharmacological treatments employed to interfere in pain behavior in different animal models was performed. Results: The treatment principles tested in animal models of neuropathic pain may have predictive validity for treatment of human neuropathies. Opioids, neurotransmitter blockers, drugs interfering with the prostaglandin syntheses as well as voltage gated sodium channel blockers and calcium channel blockers are treatment principles having efficacy and similar potency in humans and in animals. Alternative targets have been identified and have shown promising results in the validated animal models. Modulators of the glutamate system with an increased expression of glutamate re-uptake transporters, inhibition of pain promoters as nitric oxide and prostaglandins need further exploration. Modulation of cytokines and neurotrophins in neuropathic pain implies new targets for study. Further, a combination of different analgesic treatments may as well improve management of neuropathic pain, changing the benefit/risk ratio. Implications: Not surprisingly most pharmacologic principles that are tested in animal models of neuropathic pain are also found to be active in humans. Whereas many candidate drugs that were promising in animal models of neuropathic pain turned out not to be effective or too toxic in humans, animal models for neuropathic pain are still the best tools available to learn more about mechanisms of neuropathic pain. Better understanding of pathogenesis is the most hopeful approach to improve treatment of neuropathic pain.",

keywords = "Det tidligere Farmaceutiske Fakultet",

author = "Honor{\'e}, {Per Gustaf Hartvig} and Anna Basnet and Pernille Kristensen and Andersen, {Lene Munkholm} and Signe Neustrup and Pia M{\o}llgaard and Laila Eljaja and Bjerrum, {Ole Jannik}",

year = "2011",

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doi = "10.1016/j.sjpain.2011.06.002",

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T1 - Predictive validity of pharmacologic interventions in animal models of neuropathic pain

AU - Honoré, Per Gustaf Hartvig

AU - Basnet, Anna

AU - Kristensen, Pernille

AU - Andersen, Lene Munkholm

AU - Neustrup, Signe

AU - Møllgaard, Pia

AU - Eljaja, Laila

AU - Bjerrum, Ole Jannik

PY - 2011/10

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N2 - Introduction: The pathophysiologic and neurochemical characteristics of neuropathic pain must be considered in the search for new treatment targets. Breakthroughs in the understanding of the structural and biochemical changes in neuropathy have opened up possibilities to explore new treatment paradigms. However, long term sequels from the damage are still difficult to treat. Aim of the study: To examine the validity of pharmacological treatments in humans and animals for neuropathic pain. Method: An overview from the literature and own experiences of pharmacological treatments employed to interfere in pain behavior in different animal models was performed. Results: The treatment principles tested in animal models of neuropathic pain may have predictive validity for treatment of human neuropathies. Opioids, neurotransmitter blockers, drugs interfering with the prostaglandin syntheses as well as voltage gated sodium channel blockers and calcium channel blockers are treatment principles having efficacy and similar potency in humans and in animals. Alternative targets have been identified and have shown promising results in the validated animal models. Modulators of the glutamate system with an increased expression of glutamate re-uptake transporters, inhibition of pain promoters as nitric oxide and prostaglandins need further exploration. Modulation of cytokines and neurotrophins in neuropathic pain implies new targets for study. Further, a combination of different analgesic treatments may as well improve management of neuropathic pain, changing the benefit/risk ratio. Implications: Not surprisingly most pharmacologic principles that are tested in animal models of neuropathic pain are also found to be active in humans. Whereas many candidate drugs that were promising in animal models of neuropathic pain turned out not to be effective or too toxic in humans, animal models for neuropathic pain are still the best tools available to learn more about mechanisms of neuropathic pain. Better understanding of pathogenesis is the most hopeful approach to improve treatment of neuropathic pain.

AB - Introduction: The pathophysiologic and neurochemical characteristics of neuropathic pain must be considered in the search for new treatment targets. Breakthroughs in the understanding of the structural and biochemical changes in neuropathy have opened up possibilities to explore new treatment paradigms. However, long term sequels from the damage are still difficult to treat. Aim of the study: To examine the validity of pharmacological treatments in humans and animals for neuropathic pain. Method: An overview from the literature and own experiences of pharmacological treatments employed to interfere in pain behavior in different animal models was performed. Results: The treatment principles tested in animal models of neuropathic pain may have predictive validity for treatment of human neuropathies. Opioids, neurotransmitter blockers, drugs interfering with the prostaglandin syntheses as well as voltage gated sodium channel blockers and calcium channel blockers are treatment principles having efficacy and similar potency in humans and in animals. Alternative targets have been identified and have shown promising results in the validated animal models. Modulators of the glutamate system with an increased expression of glutamate re-uptake transporters, inhibition of pain promoters as nitric oxide and prostaglandins need further exploration. Modulation of cytokines and neurotrophins in neuropathic pain implies new targets for study. Further, a combination of different analgesic treatments may as well improve management of neuropathic pain, changing the benefit/risk ratio. Implications: Not surprisingly most pharmacologic principles that are tested in animal models of neuropathic pain are also found to be active in humans. Whereas many candidate drugs that were promising in animal models of neuropathic pain turned out not to be effective or too toxic in humans, animal models for neuropathic pain are still the best tools available to learn more about mechanisms of neuropathic pain. Better understanding of pathogenesis is the most hopeful approach to improve treatment of neuropathic pain.

KW - Det tidligere Farmaceutiske Fakultet

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DO - 10.1016/j.sjpain.2011.06.002

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EP - 184

JO - Scandinavian Journal of Pain

JF - Scandinavian Journal of Pain

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ER -