Areas of Interest

Research Interests

Mechanisms driving chronic pain-related hyperexcitability in nociceptive sensory neurons

After spinal cord injury, peripheral nerve damage, or chemotherapy, injury-detecting sensory neurons (primary nociceptors) switch from an electrically silent state to a hyperexcitable state that can result in the spontaneous firing of action potentials. This spontaneous activity has been shown to be correlated with chronic pain, and selective suppression of nociceptor hyperactivity by antisense knockdown of a sensory-neuron-specific Na+ channel (Nav1.8) proved to be sufficient to reduce neuropathic pain.

My research employs electrophysiological (patch-clamp) and behavioral approaches to define intracellular signaling pathways that induce and maintain the pain-related spontaneous activity in nociceptors. Of particular interest to my work are the roles of cyclic AMP dependent pathways and circulating cytokines such as MIF (Macrophage Migration Inhibitory Factor) on the generation and maintenance of this nociceptor hyperactive state.

Advances in the knowledge of the molecular signaling maintaining the nociceptor hyper-excitable state are fundamental as they provide new targets to develop efficient therapies, other than opioids, to alleviate chronic pain.

Publications

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  • Lopez ER, Carbajal AG, Tian JB, Bavencoffe A, Zhu MX, Dessauer CW, Walters ET. (2021).  Serotonin enhances depolarizing spontaneous fluctuations, excitability, and ongoing activity in isolated rat DRG neurons via 5-HT 4 receptors and cAMP-dependent mechanisms. Neuropharmacology, 184:108408.
  • Garza Carbajal A, Bavencoffe A, Walters ET, Dessauer CW. (2020). Depolarization-Dependent C-Raf Signaling Promotes Hyperexcitability and Reduces Opioid Sensitivity of Isolated Nociceptors after Spinal Cord Injury. J Neuroscience, 40, 6522-6535.
  • Gkika* D, Lolignier* S, Grolez GP, Bavencoffe A, Shapovalov G, Gordienko D, Kondratskyi A, Meleine M, Prival L, Chapuy E, Etienne M, Eschalier A, Shuba Y, Skryma R, Busserolles J, Prevarskaya N. (2020). Testosterone-androgen receptor: The steroid link inhibiting TRPM8-mediated cold sensitivity. Federation of Am Soc Experimental Biology, 34, 7483-7499 (*: contributed equally to this work).
  • Laumet* G, Bavencoffe* A, Edralin JD, Huo XJ, Walters ET, Dantzer R, Heijnen CJ, Kavelaars A. (2020). Interleukin-10 resolves pain hypersensitivity induced by cisplatin by reversing sensory neuron hyperexcitability. Pain, 161, 2344–2352 (*: contributed equally to this work).
  • Berkey S, Herrera J, Odem MA, Rahman S, Cheruvu SS, Cheng X, Walters ET, Dessauer CW, Bavencoffe† AG. (2019). EPAC1 and EPAC2 promote nociceptor hyperactivity associated with chronic pain after spinal cord injury. Neurobiology of Pain, 7, 100040 (†: corresponding author).
  • Odem MA, Bavencoffe AG, Cassidy RM, Lopez  ER, Tian J, Dessauer CW, Walters ET. (2018). Isolated nociceptors reveal multiple specializations for generating irregular ongoing activity associated with ongoing pain. Pain, 159, 2347-2362.
  • Luo J, Bavencoffe A, Yang P, Feng J, Yin S, Qian A, Yu W, Liu S, Gong X, Cai T, Walters ET, Dessauer CW, Hu H. (2017). Zinc inhibits TRPV1 to alleviate chemotherapy-induced neuropathic pain. J Neuroscience, 38, 474-483.
  • Bavencoffe* A, Li* Y, Wu Z, Yang Q, Herrera J, Kennedy EJ, Walters ET, Dessauer CW. (2016). Persistent electrical activity in primary nociceptors after spinal cord injury is maintained by scaffolded adenylyl cyclase and protein kinase A and is associated with altered adenylyl cyclase regulation. J Neuroscience, 36, 1660-1668 (*: contributed equally to this work).
  • Zhou MH, Bavencoffe A, Pan HL. (2015). Molecular basis of regulating high voltage-activated calcium channels by S-nitrosylation. J Biological Chemistry, 290, 30616-30623.
  • Efendiev* R, Bavencoffe* A, Hu H, Zhu MX, Dessauer C.W. (2012) Scaffolding by A-kinase anchoring protein enhances functional coupling between adenylyl cyclase and TRPV1 channel. J Biological Chemistry, 288, 3929-37 (*: contributed equally to this work).
  • Bavencoffe* A, Kondratskyi* A, Gkika D, Mauroy B, Shuba Y, Prevarskaya N, and Skryma R. (2011). Complex regulation of the TRPM8 cold receptor channel: role of arachidonic acid release following M3 muscarinic receptor stimulation. J Biological Chemistry, 286, 9849-9855 (*: contributed equally to this work).
  • Bavencoffe* A, Gkika* D, Kondratskyi A, Beck B, Borowiec AS, Bidaux G, Busserolles J, Eschalier A, Shuba Y, Skryma R, Prevarskaya N. (2010). The transient receptor potential channel TRPM8 is inhibited via the alpha2A adrenoreceptor signaling pathway. J Biological Chemistry, 285, 9410-9419 (*: contributed equally to this work).
  • Lallet* H, Roudbaraki* M, Bavencoffe A, Mariot P, Gackière F, Bidaux G, Urbain R, Gosset P, Delcourt P, Slomianny C, Dewailly E, Mauroy B, Bonnal JL, Skryma R, Prevarskaya N.  (2009).  Intermediate-conductance Ca2+-activated K+ channels (IKCa1) regulate human prostate cancer cells proliferation via a close control of calcium entry. Oncogene, 28, 1792–1806 (*: contributed equally to this work).
  • Gackière F, Bidaux G, Delcourt P, Van Coppenolle F, Katsogiannou M, Dewailly E, Bavencoffe A, Tran Van Chuoï-Mariot M, Mauroy B, Prevarskaya N, Mariot P.  (2008).  CaV3.2 T-type calcium channels are involved in calcium-dependent secretion of neuroendocrine prostate cancer cells. J Biological Chemistry, 283, 10162-10173.
  • Beck B, Bidaux G, Bavencoffe A, Lemonnier L, Thebault S, Shuba Y, Barrit G, Skryma R, Prevarskaya N. (2006). Prospects for prostate cancer imaging and therapy using high-affinity TRPM8 activators. Cell Calcium, 41, 285 – 294.
  • Thebault* S, Lemonnier* L, Bidaux* G, Flourakis M, Bavencoffe A, Gordienko D, Roudbaraki M, Delcourt P, Panchin Y, Shuba Y, Skryma R, Prevarskaya N.  (2005).  Novel role of cold/menthol-sensitive transient receptor potential melastatine family member 8 (TRPM8) in the activation of store-operated channels in LNCaP human prostate cancer epithelial cells. J Biological Chemistry, 280, 39423-39435 (*: contributed equally to this work).

BOOK CHAPTERS

  • Bavencoffe A, Zhu MX, Tian JB. (2017). New aspects of the contribution of ER to SOCE regulation: TRPC proteins as a link between plasma membrane ion transport and intracellular Ca2+ stores. Groschner K., Graier W., Romanin C. (eds) Store-Operated Ca²⁺ Entry (SOCE) Pathways. Adv Exp Med Biol, vol 993, Springer, Chapter 13, pp 239-255.
  • Bavencoffe A, Chen S-R, and Pan HL. (2014).  Chapter one – Regulation of nociceptive transduction and transmission by nitric oxide. IN Vitam Horm; 96: 1-18. L Gerald, editor. Academic Press.
  • Bavencoffe A, Zhu MX. (2012). TRPC proteins as a link between plasma membrane ion transport and intracellular Ca2+ stores. Groschner, K., Graier, W.F. and Romanin C. (eds), Store-Operated Ca2+ Entry (SOCE) Pathways: Emerging Signaling Concepts, Springer Press, Vienna, Austria, Chapter 12, pp.163-175.