A Healthesystems publication

Winter 2017
New Pathways in Pain Management: Novel Non-Opioid Medications

Fast Focus: As opioids continue to cause significant safety and cost concerns, drug developers have gained traction experimenting with new entities that target non-opioid pain neuropathways in the brain, which could potentially deliver safer alternatives for pain relief.

An estimated 100 million Americans suffer from chronic pain1, and as the devastating impacts of the opioid epidemic continue to reverberate, there remains a significant and unmet need for non-opioid pain medications that can safely and effectively
manage pain, without presenting the risks posed by opioids.

One trending model drug developers are employing to meet this need is the creation of new medications that reduce pain by targeting different neurochemcial pain pathways in the brain, going beyond traditional opioid pathways.


Opioid medications produce their analgesic effects by binding to special opioid receptors in the brain, triggering nerve cells to reduce pain messages sent to the brain. However, stimulating these opioid receptors is also what leads to adverse drug effects, such as respiratory depression, nausea, and importantly, the euphoric high that can eventually contribute to dependence, misuse, and abuse.

Despite the risks involved, opioids have remained popular because this mechanism of action is incredibly effective in providing pain relief. But as science continues to progress, researchers have increasingly been targeting other neuropathways in the brain that play active roles in the transmission of pain.


The FDA recently granted Fast Track designation to tanezumab, a non-opioid biologic currently in Phase 3 development for the treatment of chronic low-back pain and osteoarthritis.2 Tanezumab is a special antibody that targets, binds to, and inhibits nerve growth factor (NGF). NGF is an important mediator of pain initiation and maintenance, and researchers believe pharmacotherapies that target this pathway could show significant promise in the treatment of pain.3 Clinical trials for tanezumab are expected to produce results in 2018, and tanezumab’s Fast Track designation increases collaboration between drug developers and the FDA, which could improve the drug’s chances of FDA approval as the FDA would offer more insight and feedback.

To qualify for Fast Track status, drugs must treat unmet medical needs. The FDA’s decision to Fast Track tanezumab indicates the agency’s belief that drugs like tanezumab, which target non-opioid receptors involved in the sensation of pain, have the potential to effectively treat pain with fewer risks than currently available opioid medications.

This potentially opens the door to more investment in drugs that target non-opioid pain neuropathways, which could lead to a wave of new pain medications.


The field of neuroscience is incredibly complex, but researchers have been studying a wide range of other neuropathways that help transmit pain. In some cases, they have developed compounds that can affect those neuropathways to impact pain, and an exploration of these alternatives may serve to benefit patients in the near future, if these products prove safe and effective. (View the infographic below for an overview of current research being undertaken in neuropathways, and associated molecules in development.)


Novel, non-opioid pain medications could potentially offer patients fewer risks with significant improvements in quality of life. However, it must be acknowledged that with new pathways come new challenges. These novel medications may come with their own adverse effects, and the interconnected nature of neuropathways could lead to such drugs significantly impacting other systems within the body.

As novel products such as tanezumab eventually become available, clinical evidence will ultimately guide prescribing as it relates to pain and workplace injury. If these novel agents disrupt the pain therapy landscape in any significant way, the industry may see treatment guidelines shift to consider their role in treatment. Furthermore, the introduction of such new, high-cost specialty drugs could increase spending. It is therefore imperative that we remain vigilant for further drug developments as they have the potential to change our industry.




1 -Summary. Institute of Medicine. 2011. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. The National Academies Press. doi: 10.17226/13172.
2 -Pfizer and Lilly Receive FDA Fast Track Designation for Tanezumab. [Press release]. June 13, 2017. http://press.pfizer.com/press-release/pfizer-and-lilly-receive-fda-fast-track-designation-tanezumab
3 -Chang DS, Hsu E, Hottinger DG, Cohen SP. Anti-nerve growth factor in pain management: current evidence. Journal of Pain Research. June 2016; 9:373-383. doi:10.2147/JPR.S89061.
4 -Vriens J, Nilius B, Voets T. Peripheral thermosensation in mammals. Nature Reviews Neuroscience. July 2014. 15; 573–589. doi:10.1038/nrn3784.
5 -Almansa C, Vela JM. Selective sigma-1 receptor antagonists for the treatment of pain. Future Med Chem. June 2014. 6(10):1179-99. doi: 10.4155/fmc.14.54.
6 -Abdel-Magid, AF. Treating Pain with Somatostatin Receptor Subtype 4 Agonists. ACS Med Chem Lett. Feb 2015. 12; 6(2): 110–111. doi: 10.1021/ml500538a
7 -Miller RE, Tran PB, Das R, et al. CCR2 chemokine receptor signaling mediates pain in experimental osteoarthritis. Proc Natl Acad Sci U S A. Dec 2012. 11; 109(50): 20602–20607. doi: 10.1073/pnas.1209294110
8 -King GF, Vetter I. No gain, no pain: NaV1.7 as an analgesic target. ACS Chem Neurosci. Sep 2014. 17;5(9):749-51. doi: 10.1021/cn500171p
9 -Kanju P, Chen Y, Lee W, et al. Small molecule dual-inhibitors of TRPV4 and TRPA1 for attenuation of inflammation and pain. Sci. Rep. June 2016. 6, 26894; doi: 10.1038/srep26894.
10 -Centrexion Therapeutics Provides Updates and Advancements for Pipeline of Chronic Pain Treatments. [Press release]. July 2017. http://www.businesswire.com/news/home/20170718005375/en/Centrexion-Therapeutics-Updates-Advancements-Pipeline-Chronic-Pain.
11 -Selective Inhibitors of Nav1.7 for the Treatment of Pain. Xenon Pharma website. https://www.xenon-pharma.com/product-candidates/pain/pain-genentech/. Accessed August 15, 2017.
12 -TV-45070: A Topical Sodium Channel Inhibitor for the Treatment of Pain. Xenon Pharma website. https://www.xenon-pharma.com/product-candidates/pain/pain-teva/. Accessed August 15, 2017.
13 -Mundipharma and Purdue Pharma Expand Pain Pipeline with New Deal for First-in-Class Sigma-1 Antagonist (S1A or MR309/E-52862) from ESTEVE. [Press release]. May 16, 2016. http://www.purduepharma.com/news-media/2016/05/mundipharma-and-purdue-pharma-expand-pain-pipeline-with-new-deal-for-first-in-class-sigma-1-antagonist-s1a-or-mr309e-52862-from-esteve/
14 -Centrexion Therapeutics Announces Highly Statistically Significant Topline Results from Phase 2b Study of CNTX-4975 in Patients with Knee Osteoarthritis Pain. [Press release]. December 13, 2016. http://centrexion.com/wp-content/uploads/2016/12/CNTRX_12_13.pdf
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