Anna P. Malykhina, Ph.D.

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