Giving priority to preclinical pain measures resistant to existing drugs for developing innovative analgesics

Preclinical Research & Development Chronic pain is a major health and socioeconomic burden because of its high prevalence, negative influence on patients' physical and/or emotional conditions, and huge costs to society. The responses of chronic pain patients to analgesic therapies vary substantially from individual to individual, and no more than a minority of chronic pain patients with various etiologies such as neuropathy and inflammation are, in fact, successfully relieved by existing drugs including opioid analgesics, nonopioid analgesics, antiepileptics, and antidepressants. The large primary unmet medical need would therefore be the patient domain that does not respond well to existing drugs. Accordingly, the expected profile for innovative analgesics would not be efficacy in the responder patient domain, but significant efficacy in patients with existing drug-resistant chronic pain. Meanwhile, the current gold standard in preclinical pain measures for the screening of analgesic candidates is existing drug-sensitive pain measures in animal models of chronic pain. Analgesic candidates screened using such preclinical pain measures during the last decades have been far from fulfilling the expected profile for innovative analgesics. Given that it is unlikely that such existing drug-sensitive pain measures are the best approach to developing innovative analgesics, one of the other approaches would be giving priority to existing drug-resistant pain measures in preclinical research. This review introduces potentially applicable existing drug-resistant pain measures published so far and suggests that the use of them would lead to the development of innovative analgesics.