http://orcid.org/0000-0001-8104-1493
It has come to our attention that two recent papers [Citation1,Citation2] that appeared in Expert Opinion on Therapeutic Patents (EOTP) covering the patent landscape on novel approaches to target neuropathic pain have failed to include and discuss our discovery that A3 adenosine receptor (AR) agonists reverse or prevent chronic pain in animal models. The approach we have introduced is novel, and it avoids many of the liabilities associated with established treatment of neuropathic pain, as described in a recent review paper [Citation3]. The protective effect of A3AR agonists in several models of chronic neuropathic pain including that caused by widely used chemotherapeutic agents [Citation4,Citation5] does not desensitize over time with constant drug exposure, and there is no risk of addiction [Citation6]. Highly selective A3AR agonists that we have developed [Citation7] lack the cardiovascular side effects known for other AR agonists, such as A1AR agonists [Citation8], which also provide pain relief. We have explored the mechanistic basis for this dramatic protective effect of A3AR agonists in chronic neuropathic pain. It is dependent on GABAergic transmission, but not cannabinoid or opioid receptors, in the spinal cord, and protective effects are induced by A3AR in peripheral sensory neurons and in the brain. Peripherally administered A3AR agonists correct an imbalance in dorsal horn cytokines, oxidative pathways, and glutamatergic transmission associated with the pain state. A3AR agonists are also protective in other pain models, such bone cancer pain [Citation6,Citation9,Citation10]. Thus, A3AR agonists promise to be safe and effective in the treatment of chronic neuropathic pain of various etiologies.
We are not sure of the reason behind this omission. Since our patents are published [Citation11–Citation13], an accurate patent search, which we are sure must have been carried out by the authors in preparation of their review articles, would have identified our patents. It would have been be highly desirable for the A3AR agonists to be included, since the authors are providing expert opinions and are covering new perspectives. We value the contribution of EOTP to the field. Thus, we wish to bring a major omission to the attention of the readership interested in the current patent landscape in neuropathic pain.
Declaration of interest
Daniela Salvemini has a financial interest in Biointervene.
References
- do Couto Maia R. Recent trends in neuropathic pain patents. Expert Opin Ther Pat. 2017;27: 539-546. DOI:10.1080/13543776.2017.1273349
- Pina LTS, Gouveia DN, Costa JS, et al. New perspectives for chronic pain treatment: a patent review (2010-2016). Expert Opin Ther Pat. 2017;27:787–796. DOI:10.1080/13543776.2017.1297425
- Janes K, Jacobson KA, Symons-Liguori AM, et al. Identification of A3 adenosine receptor agonists as novel non-narcotic analgesics. Br J Pharmacol. 2016;173:1253–1267.
- Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain. 1988;33:87−107.
- Chen Z, Janes K, Chen C, et al. Controlling murine and rat chronic pain through A3 adenosine receptor activation. Faseb J. 2012;26:1855–1865.
- Little JW, Ford A, Symons-Liguori AM, et al. Endogenous adenosine A3 receptor activation selectively alleviates persistent pain states. Brain. 2015;138:28–35.
- Tosh DK, Crane S, Chen Z, et al. Rigidified A3 adenosine receptor agonists: 1-Deaza modification maintains high in vivo efficacy. ACS Med Chem Lett. 2015;6:804–808.
- Luongo L, Petrelli R, Gatta L, et al. 5′-Chloro-5′-deoxy-ENBA, a potent and selective adenosine A1 receptor agonist, alleviates neuropathic pain in mice through functional glial and microglial changes without affecting motor and cardiovascular functions. Molecules. 2012;17:13712–13726.
- Varani K, Vincenzi F, Targa M, et al. The stimulation of A3 adenosine receptors reduces bone-residing breast cancer in a rat preclinical model. Eur J Cancer. 2013;49:482–491.
- Yan H, Zhang E, Feng C, et al. Role of A3 adenosine receptor in diabetic neuropathy. J Neurosci Res. 2016;94:936–946.
- Jacobson KA, Tosh DK, Salvemini D A3 adenosine receptor agonists. WO080940. 2015.
- Salvemini D Use of A3 adenosine receptor agonists for treatment of neuropathic pain. US9132131B2. 2015.
- Salvemini D Inhibition of opioid antinociceptive tolerance and withdrawal in nociceptive pain therapy. US0087613. 2015.