Virginia Seybold, PhD

Professor Emeritus, Department of Neuroscience

Professor Emeritus, Department of Neuroscience


Research Summary/Interests

Cellular mechanisms underlying hyperalgesia

Although acute pain is an important adaptive mechanism that alerts an organism to tissue injury and initiates behavior to avoid further injury, chronic pain seems to serve no useful purpose. My research program addresses mechanisms underlying hyperalgesia, the increased sensation of pain that is felt following tissue injury. Mechanisms for hyperalgesia are explored at both ends of sensory neurons: at the peripheral process, where the signal of a noxious stimulus is first transduced, and in the spinal cord, where the first synapse in the pathway for sensation of pain is located. Sensitization of sensory neurons occurs in conjunction with hyperalgesia.

Sensitization is the cellular process responsible for the increased response of sensory neurons to noxious stimuli. The mechanism underlying sensitization, however, is not understood. Using activity-dependent fluorescent dyes, we are exploring whether substances generated in injured tissue by cells of the immune system act directly on sensory neurons to enhance the response of these neurons to noxious stimuli. In addition, molecular biology is used to study plasticity in the expression of peptides, neurotransmitters and receptors in sensory neurons in conjunction with inflammation.

Recently, it has been shown that neurons in the spinal cord exhibit increased excitability in parallel with hyperalgesia following peripheral injury. The second area of my research addresses whether peptides released from sensory neurons contribute to the increased excitability of spinal neurons. Modulation of the flexor reflex by receptor antagonists is used to assess the role of specific transmitters in the hyperexcitability of spinal neurons that accompanies peripheral inflammation and hyperalgesia. Biochemical studies of spinal neurons in vitro are used to explore the intracellular pathways by which receptor activation leads to a change in neuronal excitability.


Khasabova, IA, Uhelski, M, Khasabov, SG, Gupta, K, Seybold, VS & Simone, DA 2019, ‘Sensitization of nociceptors by prostaglandin E(2)-glycerol contributes to hyperalgesia in mice with sickle cell disease’ Blood, vol. 133, no. 18, pp. 1989-1998. doi:

Khasabova, IA, Khasabov, SG, Olson, JK, Uhelski, ML, Kim, AH, Albino-Ramírez, AM, Wagner, CL, Seybold, VS & Simone, DA 2019 ‘Pioglitazone, a PPAR? agonist, reduces cisplatin-evoked neuropathic pain by protecting against oxidative stress’ Pain, vol. 160, no. 3, pp. 688-701.

Khasabova, IA, Yao, X, Paz, J, Lewandowski, CT, Lindberg, AE, Coicou, L, Burlakova, N, Simone, DA & Seybold, VS. 2014 ‘JZL184 is anti-hyperalgesic in a murine model of cisplatin-induced peripheral neuropathy’ Pharmacol Res, vol. 90, pp. 67-75.

Khasabova, IA, Holman, M, Morse, T, Burlakova, N, Coicou, L, Harding-Rose, C, Simone, DA & Seybold, VS 2013 ‘Increased anandamide uptake by sensory neurons contributes to hyperalgesia in a model of cancer pain’ Neurobiol Dis, vol. 58, pp. 19-28.

Khasabova, IA, Khasabov, S, Paz, J, Harding-Rose, C, Simone, DA & Seybold, VS 2012, ‘Cannabinoid type-1 receptor reduces pain and neurotoxicity produced by chemotherapy’ J Neurosci, vol. 32, no. 20, pp. 7091-101.

Khasabova, IA, Gielissen, J, Chandiramani, A, Harding-Rose, C, Odeh, DA, Simone, DA & Seybold, VS 2011, ‘CB1 and CB2 receptor agonists promote analgesia through synergy in a murine model of tumor pain’ Behav Pharmacol, vol. 22, no. 5-6, pp. 607-16.

Khasabova, IA, Chandiramani, A, Harding-Rose, C, Simone, DA & Seybold, VS 2011, ‘Increasing 2-arachidonoyl glycerol signaling in the periphery attenuates mechanical hyperalgesia in a model of bone cancer pain’ Pharmacol Res, vol. 64, no. 1, pp. 60-7.

Khasabova, IA, Khasabov, SG, Harding-Rose, C, Coicou, LG, Seybold, BA, Lindberg, AE, Steevens, CD, Simone, DA & Seybold, VS 2008, ‘A decrease in anandamide signaling contributes to the maintenance of cutaneous mechanical hyperalgesia in a model of bone cancer pain’ J Neurosci, vol. 28, no. 44, pp. 11141-52.

Khasabova, IA, Stucky, CL, Harding-Rose, C, Eikmeier, L, Beitz, AJ, Coicou, LG, Hanson, AE, Simone, DA & Seybold, VS 2007, ‘Chemical interactions between fibrosarcoma cancer cells and sensory neurons contribute to cancer pain’ J Neurosci, vol. 27, no. 38, pp. 10289-98.

Groth, RD, Coicou, LG, Mermelstein, PG & Seybold, VS 2007, ‘Neurotrophin activation of NFAT-dependent transcription contributes to the regulation of pro-nociceptive genes’ J Neurochem, vol. 102, no. 4, pp. 1162-74.