Introduction Animal disease models are predictive for signs seen in disease. They may rarely mimic all signs in a specific disease in humans with respect to etiology, cause or development. Several models have been developed for different pain states and the alteration of behavior has been interpreted as a response to external stimulus or expression of pain or discomfort. Considerable attention must be paid not to interpret other effects such as somnolence or motor impairment as a pain response and similarly not to misinterpret the response of analgesics. Neuropathic pain is caused by injury or disease of the somatosensory system. The clinical manifestations of neuropathic pain vary including both stimulus-evoked and non-stimulus evoked (spontaneous) symptoms. By pharmacological intervention, the threshold for allodynia and hyperalgesia in the various pain modalities can be modulated and measured in animals and humans. Animal models have been found most valuable in studies on neuropathic pain and its treatment. Aim of the study With these interpretation problems in mind, the present text aims to describe the most frequently used animal models of neuropathic pain induced by mechanical nerve injury. Methods The technical surgical performance of these models is described as well as pain behavior based on the authors own experience and from a literature survey. Results Nerve injury in the hind limb of rats and mice is frequently used in neuropathic pain models and the different types of lesion may afford difference in the spread and quality of the pain provoked. The most frequently used models are presented, with special focus on the spared nerve injury (SNI) and the spinal nerve ligation/transection (SNL/SNT) models, which are extensively used and validated in rats and mice. Measures of mechanical and thermal hypersensitivity with von Frey filaments and Hargreaves test, respectively, are described and shown in figures. Conclusions A number of animal models have been developed and described for neuropathic pain showing predictive value in parallel for both humans and animals. On the other hand, there are still large knowledge gaps in the pathophysiologic mechanisms for the development, maintenance and progression of the neuropathic pain syndrome Implications Better understanding of pathogenic mechanisms of neuropathic pain in animal models may support the search for new treatment paradigms in patients with complex neuropathic pain conditions.
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.
Aims The clinical relevance of adding the acetylcholinesterase inhibitor donepezil to existing gabapentin treatment in patients with post-traumatic neuropathic pain was explored in this open-label study. The two drugs have previously shown synergism following co-administration in nerve-injured rats [1,2]. Methods The study comprised two consecutive periods of minimum six weeks: (1) titration of gabapentin until highest tolerable dose or maximum 24GG mg daily; and (2) addition of donepezil 5 mg once daily to the fixed gabapentin dose. Efficacy and tolerability were assessed by ratings of pain intensity, questionnaires for pain and health-related quality of life, and reporting of adverse events and analgesic rescue medication. Pain scores were also analyzed using mixed-effects analysis (i.e. incorporating inter-subject variability) with the software NONMEM. Results Eight patients commenced treatment with donepezil upon the gabapentin titration period, of which two withdrew due to adverse events. Addition of donepezil reduced pain by >35% in four of six patients compared to gabapentin monotherapy. Mixed-effects analysis revealed that pain scores were significantly lower during co-administration (p < 0.05 combination vs. monotherapy). Donepezil was well tolerated in combination with gabapentin. At the end of study, three patients wished to continue combination therapy with gabapentin and donepezil. Conclusions Donepezil may provide additional analgesia to neuropathic pain patients with insufficient pain relief from gabapentin as monotherapy. Further confirmation in controlled clinical trials is justified. Mixed-effects analysis was sensitive enough to detect statistically significant effects, showing its usefulness in small-scale trials and/or when data is associated with high variability.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.