Anna P. Malykhina, Ph.D.

faculty photo
Assistant Professor of Urology in Surgery
Department: Surgery
Graduate Group Affiliations

Contact information
Division of Urology
University of Pennsylvania
Glenolden Research Laboratory
500 South Ridgeway Avenue, Room 158
Glenolden, PA 19036
Office: (267) 350 9606
Fax: (267) 350 9609
Education:
M.S. (Biology/Physiology)
Belorussian State University, Minsk, Belarus, 1993.
Ph.D. (Physiology/Electrophysiology)
Institute of Radiobiology, National Academy of Sciences, 1998.
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Description of Research Expertise

Research Interests

Dr. Malykhina`s research interests center on neurophysiology of functional pelvic disorders with chronic pelvic pain syndrome, with particular emphasis on the mechanisms underlying the processing of sensory nociceptive information by the central and peripheral nervous systems. The current projects in the laboratory study the alterations in the function of voltage gated Na+ channels and TRPV1 channels in primary sensory neurons, release of pro-inflammatory neurotransmitters and neuropeptides in the periphery as well as inflammation-induced channelopathies in gastrointestinal and genitourinary smooth muscle.

Key words
Functional pelvic disorders, chronic pelvic pain, pelvic organ cross-sensitization, neurogenic inflammation in the pelvis, neurogenic bladder, TRPV1 and Na channels, primary sensory neurons

Description of Research
Chronic pelvic pain is a major symptom of many complex clinical conditions, including painful bladder syndrome (PBS), non-bacterial chronic prostatitis, irritable bowel syndrome (IBS), vulvodynia. Pelvic organ cross-sensitization is considered as one of the factors contributing to chronic pelvic pain of unidentified origin. Cross-sensitization in the pelvis implies the transmission of noxious stimuli from a diseased pelvic organ to an adjacent normal structure resulting in the occurrence of functional (rarely structural) changes in the latter. Distribution of sensitization in the pelvis mainly occurs via shared sensory neural pathways at prespinal, spinal and supraspinal levels (reviewed in Malykhina A.P. Neural mechanisms of pelvic organ cross-sensitization (2007). Neuroscience, Review). We use neuroanatomical, immunohistochemical, electrophysiological and neuropharmacological methods to characterize the role of sensory neural pathways in cross-sensitization between pelvic organs and chronic pelvic pain.
Primary sensory neurons express a vast population of membrane receptors and produce different neuropeptides, persistently or transiently sensitizing the DRG and spinal cord under pathological conditions. Activation of sensory neurons innervating pelvic organs may lead to up-regulation of some neuromodulators and/or down-regulation of others. Those substances eventually can be released at the peripheral terminals of axons making direct (via convergent DRG somata) or indirect (via spinal cord pathways) connections with adjacent pelvic structures to provoke the development of visceral hyperalgesia. When antidromic impulses arrive in the periphery of the area innervated by activated primary afferent nociceptors, they trigger the release of neuromodulators and neuropeptides. Inflammation evoked by substances released from sensory nerve terminals is referred to as “neurogenic inflammation”. Ongoing experiments study the changes in neurotransmission in the irritated pelvic organs, DRG, spinal cord, and the brain concurrently to follow the patterns and time-dependence of the synthesis and release of major neuropeptides
Technical approaches include survival rodent surgeries, use of retrograde fluorescent tracers, immunohistochemistry, in vivo and in vitro contractility studies, patch and voltage clamp techniques, primary neuronal and smooth muscle cell culture, ELISA, Western blotting, conventional and quantitative RT-PCR.

Rotation Projects
1. Role of sensory afferent pathways in the development of neurogenic inflammation in the pelvis and neuropathic pain
2. Modulation of pelvic pain resulted from neurogenic cystitis by ovarian hormones


Laboratory Personnel

Qi Lei, MD, PhD – Postdoctoral Fellow
Tirsit Asfaw, MD - Postdoctoral Urogynecology Fellow
Xiao-Qing Pan, MD – Research Specialist C
Shaohua Chang, PhD – Research Specialist C
Thomas Mathai, BS – Research Specialist A
Jessica Gonzalez, BS – Laboratory Technician C
Jocelyn McCabe, BS – Administrative Assistant

Selected Publications

Lei Q, Pan XQ, Villamor AN, Asfaw TS, Chang S, Zderic SA, Malykhina AP : Lack of transient receptor potential vanilloid 1 channel modulates the development of neurogenic bladder dysfunction induced by cross-sensitization in afferent pathways J Neuroinflammation 10(1): 3, January 2013.

Malykhina A.P., Lei Q., Erickson C.S., Epstein M.L., Saban M.R., Davis C.A., Saban R. : VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity. BMC Physiol 12(1): 15, December 2012.

Malykhina A.P., Qin C., Lei Q., Pan X.Q., Greenwood-Van Meerveld B., Foreman R.D. : Differential effects of intravesical resiniferatoxin on excitability of bladder spinal neurons upon colon-bladder cross-sensitization. Brain Res S0006-8993(12)(12): 01778-7, November 2012.

Arya L.A., Northington G.M., Asfaw T.S., Harvie H., Malykhina A. : Evidence of bladder oversensitivity in the absence of an infection in premenopausal women with a history of recurrent urinary tract infections. BJU Int 110(2): 247-51, July 2012.

Lei Q., Malykhina A.P. : Colonic inflammation up-regulates voltage-gated sodium channels in bladder sensory neurons via activation of peripheral transient potential vanilloid 1 receptors. Neurogastroenterol Motil 24(6): 575-85, June 2012.

Malykhina A.P., Wyndaele J.J., Andersson K.E., de Wachter S., Dmochowski R.R.: Do the urinary bladder and large bowel interact, in sickness or in health? ICI-RS 2011. Neurourol Urodyn 31(3): 352-8, March 2012.

Cory L., Harvie H.S., Northington G.M., Malykhina A., Whitmore K., Arya L.A.: Association of neuropathic pain with bladder, bowel and cataetrophizing symptoms in women with bladder pain syndrome. J Urol 187(2): 503-7, February 2012.

Asfaw T.S., Hypolite J., Northington, G.M., Arya L.A., Wein A. J., Malykhina A.P.: Acute colonic inflammation triggers detrusor instability via activation of TRPV1 receptors in a rat model of pelvic organ cross-sensitization. Am J Physiol Regul Integr Comp Physiol 300(6): R1392-1400, June 2011.

1.Pan X.-Q., Gonzalez J.A., Chang S., Chacko S, Wein A., Malykhina A.P.: Experimental colitis triggers the release of substance P and calcitonin gene-related peptide in the urinary bladder via TRPV1 signaling pathways. Exp Neurology May 2010.

Qin C, Malykhina AP, Thompson AM, Farber JP, Foreman RD. : Cross-organ sensitization of thoracic spinal neurons receiving noxious cardiac input in rats with gastroesophageal reflux. Am J Physiol Gastrointest Liver Physiol 8: [Epub ahead of print] April 2010.

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Last updated: 01/14/2013
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