Predictive validity of pharmacologic interventions in animal models of neuropathic pain

IntroductionThe 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 studyTo examine the validity of pharmacological treatments in humans and animals for neuropathic pain.MethodAn overview from the literature and own experiences of pharmacological treatments employed to interfere in pain behavior in different animal models was performed.ResultsThe 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.ImplicationsNot 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.

► Paintreatments for humans have been developed from neuropathic pain models in animals.
► Sodium and calcium channel blockers, opioids, enhancers of serotonin, noradrenaline, GABA, or acetylcholine, and steroids may reduce pain in humans.
► Substances acting on targets like sortilin, glutamate transporters, nitric oxide, cytokines and neurotrophins might represent future treatment principles.
► A combination of analgesic treatment principles might improve control of neuropathic pain.
► Combination pharmacotherapy might also improve benefit and reduce risk of dose related adverse effects.