A Revolution
in Pain Medication

Unmet Needs of Pain Medication

Pain is a universal human experience. It can manifest in various forms, including physical, emotional, or psychological pain.
Every single human is, has or will experience pain at some point of his/her life.

Pain is commonly classified as acute or chronic. Acute pain is short-lived and essential for the maintenance of our physical integrity, whereas chronic pain persists beyond the normal time of healing and adversely affects well-being. Pain is classified into three main levels based on its intensity: mild, moderate, and severe.

While mild pain is usually treated with «safe» analgesics such as paracetamol, higher levels of pain require stronger analgesics, such as opioids, which are effective but have significant drawbacks and potential risks, including addiction, overdose, respiratory depression and withdrawal symptoms.

Untreated pain can have far-reaching effects beyond the immediate discomfort: sleep disorder, depression, social isolation. Most importantly, inadequately treated pain can contribute to development of chronic pain; a condition that affects 20% of the world population with a substantial economic burden.

Pain medication is plagued with severe adverse effects. While mild analgesics such as paracetamol are generally considered safe within a well-defined dosing regimen, opioids present risks of addiction even at low doses, leading many patients to decline opioids and instead deal with the pain (which in turn usually delays full recovery, for example by impeding physical therapy). Some antiepileptic drugs, widely used in the treatment of neuropathic pain can also lead to misuse and abuse.

Opioids represent 32% of the pain medication market. They are a part of the overall need, but are highly representative of the issues to be solved:

Despite their initial efficacy, opioids lose efficacy when administered repeatedly (an issue called tolerance), which make them woefully unsuited to treating chronic pain (20% of the population are
estimated to suffer from various kinds of chronic pains), and increase the risk of addiction as the patients increase dosage to maintain an equivalent level of pain management.

Addiction: opioids such as morphine, fentanyl, or the less-potent tramadol, are well-known to be highly addictive, just as their namesake is (opium). This leads to major health issues of addiction, substance abuse, overdoses, and death. The so-called «Opioid Crisis» in theUSA kills over 50,000 people each year, from opioid-related overdoses only. It is a fast-accelerating phenomenon.

There is an urgent need to develop new solutions for pain medication and management, based on a new approach.
This is Tafalgie’s mission.

The TAFA4 Protein

TAFA4 is a small endogeneous neurokinin protein secreted by C-low threshold mechanoreceptors (C-LTMRs).

Initially characterized in 1939, C-LTMRs were previously thought to only mediate pleasant touch sensation. Research by the Moqrich team identified TAFA4 as a molecular marker of C-LTMRs, and demonstrated that this molecule is a strong modulator of pain transmission.

Specifically, the loss of TAFA4 leads to exacerbation and long-lasting injury-induced mechanical and chemical pain. Exogenous administration of TAFA4 enhances the spinal inhibitory tone under physiological conditions, and strongly reverses the injury-induced diminished inhibitory function of the Gating Neurons.

This endogenous protein is inherently safe (no toxicity). Moreover, preclinical studies have shown that its efficacy is not diminished by repeated administration (no tolerance).

This makes TAFA4 ideally suited for all kinds of pain, including chronic pain.

Pain Relief

The ground-breaking combination of high efficacy and absence of tolerance, mean that TAFA4 and its derivatives (our Portfolio of Leads) are perfect candidates for a genuine revolution in pain medication; a safe alternative to the current unsatisfactory options.

Moreover, the specific absence of tolerance particularly boost TAFA4’s ability to address chronic pain.


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  • Reynders, A., Jhumka, A., Gaillard, S., Hoeffel, G., Mantilleri, A. Malapert, P., Salio, C., Ugolini, S., Castets, F., Saurin, A., Serino, M. And Moqrich, A. (2023) Gut microbiota promotes pain chronicity in Myosin1A deficient male mice. (Under revision) Brain, Behavior and Immunity.
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  • Kambrun, C., Roca-Lapirot, O., Salio, C., Landry, M., Moqrich, A., and Le Feuvre, Y. (2018). TAFA4 Reverses Mechanical Allodynia through Activation of GABAergic Transmission and Microglial Process Retraction. Cell Rep 22, 2886-2897.
  • Fromy, B., Josset-Lamaugarny, A., Aimond, G., Pagnon-Minot, A., Marics, I., Tattersall, G.J., Moqrich, A., and Sigaudo-Roussel, D. (2018). Disruption of TRPV3 Impairs Heat-Evoked Vasodilation and Thermoregulation: A Critical Role of CGRP. J Invest Dermatol 138, 688-696.
  • Bautzova, T., Hockley, J.R.F., Perez-Berezo, T., Pujo, J., Tranter, M.M., Desormeaux, C., Barbaro, M.R., Basso, L., Le Faouder, P., Rolland, C., et al. (2018). 5-oxoETE triggers nociception in constipation-predominant irritable bowel syndrome through MAS-related G protein-coupled receptor D. Sci Signal 11.
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  • Reynders, A., Mantilleri, A., Malapert, P., Rialle, S., Nidelet, S., Laffray, S., Beurrier, C., Bourinet, E., and Moqrich, A. (2015). Transcriptional Profiling of Cutaneous MRGPRD Free Nerve Endings and C-LTMRs. Cell Rep 10, 1007-1019.
  • Reynders, A., and Moqrich, A. (2015). Analysis of cutaneous MRGPRD free nerve endings and C-LTMRs transcriptomes by RNA-sequencing. Genom Data 5, 132-13.
  • Francois, A., Schuetter, N., Laffray, S., Sanguesa, J., Pizzoccaro, A., Dubel, S., Mantilleri, A., Nargeot, J., Noel, J., Wood, J.N., et al. (2015). The Low-Threshold Calcium Channel Cav3.2 Determines Low-Threshold Mechanoreceptor Function. Cell Rep 10, 370-382.
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  •  Gaillard*, S., Lo-Re*, L., Mantilleri, A., Urien, L., Malapert, P., Alonso, S., Deage, M., Kambrun, C., Landry, M., Low, S.A, Scherrer, G., Alloui, A., Le Feuvre, Y., Bourinet, E. and Moqrich, A. (2014) GINIP, a new Gai interacting protein, functions as a key modulator of peripheral GABAB receptor-mediated analgesia. Neuron, Oct 1;84(1):123-136.
  • Marics, I. Malapert, P., Reynders, A., Gaillard, S. and Moqrich, A. (2014) Acute heat-evoked temperature sensation is impaired but not abolished in mice lacking TRPV1 and TRPV3 channels. Plos One, Jun 12;9(6):e99828.
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  • Bouhadfane, M., Tazerart, S., Moqrich, A., Vinay, L., and Brocard, F. (2013). Sodium-mediated plateau potentials in lumbar motoneurons of neonatal rats. J Neurosci 33, 15626-15641.
  • Gaillard*, S., Gascon*, E., Malapert, P., Liu, Y., Rodat Despoix, L., Samokhvalov, I.M, Delmas, P., Helmbacher, F., Maina, F. and Moqrich, A. (2010). HGF-Met signaling is required for Runx1 extinction and peptidergic differentiation in primary nociceptive neurons. J. Neurosc. vol 30(37), pp12414-12423.
  • Legha, W., Gaillard, S., Gascon, E., Malapert, P., Hocine, M., Alonso, S. and Moqrich, A. (2010) stac1 and stac2 genes define discrete and distinct subsets of dorsal root ganglia neurons. Gene Expression Patterns, vol 10, pp368-375.
  • Gascon, E., and Moqrich, A. (2010). Heterogeneity in primary nociceptive neurons: from molecules to pathology. Arch Pharm Res 33, 1489-1507.
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  • Peier, A.M., Reeve, A.J., Andersson, D.A., Moqrich, A., Earley, T.J., Hergarden, A.C., Story, G.M., Colley, S., Hogenesch, J.B., McIntyre, P., et al. (2002b). A heat-sensitive TRP channel expressed in keratinocytes. Science 296, 2046-2049
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