oa Editorial [Hot Topic: Analgesic Drug Discovery: Promising Future (Guest Editor: Anindya Bhattacharya)]

Chronic pain is an unmet medical need. Millions of people suffer from some form of chronic pain that often is co-morbid with cancer, diabetes, arthritis, anxiety and depression: a growing list of diseases that contribute to short/long-term disability and affect quality of life. According to American Pain Foundation, more Americans suffer from some form of chronic pain than diabetes, heart disease, stroke and cancer. Chronic pain encompasses back/neck pain, headache (migraine), visceral pain, fibromyalgia, cancer pain, neuropathic pain and pain associated with osteoarthritis or rheumatoid arthritis. Pain therapy is primarily driven by modestly effective, side-effect limiting opioid therapy although pregabalin and duloxetine with new mechanisms have gained momentum, especially for neuropathic pain and fibromyalgia. Efficacy remains the largest unmet need in the area of chronic pain. Several pharmaceutical companies have been engaged in analgesic drug discovery programs prosecuting novel targets with differentiated mechanism of actions: while the effort has greatly contributed to our overall understanding of the role of different targets (GPCRs, ion channels, enzymes) in pain physiology, clinical success has been limited. A good example of such a target is TRPV1: while the pain community has benefited immensely from selective TRPV1 antagonists, many of which have contributed in further elucidation of the role of the target in nociception, several companies have suspended clinical development of TRPV1 antagonists due to target limiting adverse events. Continued clinical failures results in short term panic by the sponsoring organizations that has precipitated in many notable pharmaceutical/biotechnology companies moving out of pain area or significantly reducing workforce in analgesic drug discovery and development. The question that I like to ask is: is the future of pain drug discovery and development really that bleak? This issue is being put forward to demonstrate that the future of pain drug discovery is not that bleak after all. One of the major challenges in the field has been lack of proper translation of preclinical pain data to the clinic. Several novel mechanisms seem to pass the test in various models of pain (acute, spontaneous, neuropathic, inflammatory, cancer, arthritis) in rodents but then fall short in early proof of concept human trials. In this issue, we have review on animal models of pain followed by more focused articles on animal models of osteoarthritic pain and fibromyalgia. Cancer pain is an area of neglect and there is a huge unmet medical need; the group from Eli Lilly focuses on that aspect in their contribution. Biologics has become an important part and parcel in our arsenal to target novel and ‘ undruggable’ targets (Druggability defined by small molecule success) and there is chapter that reviews that approach as well. The rest of the issue deals with analgesic drug targets across various target families with a view to highlight state of the research in the field. In closing, I like to thank all the contributors who have worked tirelessly with me to bring this issue to fruition.