Research Description:
Untitled Document
Dr. Murphy has a joint appointment in the Neuroscience Institute as well as the Department of Biology
Our major research interest focuses on how endogenous gonadal steroids influence
pain sensitivities. It is well established that women exhibit a higher prevalence
of temporomandibular disorders, neuropathic pain, fibromyalgia, migraine headaches
and some forms of arthritis. Furthermore, variations in hormonal levels associated
with the menstrual cycle, menopause, pregnancy and lactation influence pain
levels. The midbrain periaqueductal gray (PAG) has long been established as
an important neural structure in the endogenous descending analgesia system.
Stimulation of this region produces long lasting antinociception that is mediated,
in part, via the release of endogenous opioids. In addition to sex-based differences
in pain sensitivity, there is also a sex difference in morphine sensitivity,
such that the ED50 dose is 8 fold lower for males than for females. These differences
are not due to the pharmacokinetics of morphine, but rather, due to inherent
differences in the sensitivity of the brain to morphine. Where these differences
lie, however, is not known.
 Our research utilizes a multidisciplinary approach to examining how pain and
opioidergic neural circuits are differentially organized and activated in males
and females. Ongoing behavioral studies in the lab have demonstrated that males
and females have significantly different sensitivities to morphine in a model
of chronic inflammatory pain. Indeed, the ED50 for systemic morphine in males
is 4.5 mg/kg in comparison to >14 mg/kg in females. Current molecular studies
are examining the potential mechanisms that may contribute to sex based differences
in morphine analgesia. Using in situ hybridization along with advanced immunocytochemical
techniques, we have recently shown that the distribution of the mu and delta
opioid receptor (both protein and mRNA) is sexually dimorphic within the PAG.
 Future studies will use adeno-associated viruses to overexpress the mu opioid
receptor within the PAG of females in order to make them more ‘male-like’
in their sensitivity to opioids. Additional studies in the laboratory are examining
the organization of the descending analgesia circuit in males and females. While
this circuit has been well characterized in a variety of species, to date, how
this pathway is organized in females remains unknown. Using antero- and retrograde
tract tracing techniques, we have recently shown that the descending projections
from the PAG are sexually dimorphic both in the anatomical organization, as
well as in their activation during either acute or chronic inflammatory pain.
A second line of research in our laboratory is examining the influence of neonatal
injury on adult sensory development. All previous studies examining the impact
of neonatal injury have been conducted exclusively in males. However, males
and females differ significantly in their neuroendocrine profile during the
first week of life. In particular, males experience a surge in testosterone
that is locally converted into estrogen and ultimately results in the masculinization
of the male brain. In females, the ovaries are quiescent and intracerebral estradiol
remains low. As estradiol has been previously shown to confer neuroprotection
following CNS injury, ongoing experiments in the lab are testing the hypothesis
that the effects of neonatal injury on adult sensory thresholds are exacerbated
in female rats in comparison to males. These studies also utilize a multidisciplinary
approach, including behavioral, neuroanatomical, immunocytochemical and molecular
techniques.
Lab Personnel
Dayna Loyd, Graduate Student, biodrl@langate.gsu.edu
Xioaya Wang, Post-Doctoral Fellow, xyl88@hotmail.com
Shelby Suckrow, Undergraduate Assistant, ssuckow1@student.gsu.edu
Recent Publications:
Murphy, A.Z., Beall, E., and Snyder, N.S. Activation of the medial preoptic region and its efferents by copulation: A tract tracing and Fos immunocytochemical study. J. Comp. Neurol. (submitted).
Robertson, C.L., Puskar, A., Hoffman, G.E., Murphy, A.Z., Saraswati, M., and Fiskum, G. Physiologic progesterone reduces mitochondrial dysfunction and hippocampal cell death after traumatic brain injury in female rats. Experimental Neurology 197 (2006) 235-43.
Loyd, D. and A.Z. Murphy Sex differences in the anatomical and functional organization of the midbrain periaqueductal gray-rostral ventromedial medullary pathway: A potential circuit mediating the sexually dimorphic actions of morphine. J. Comp. Neurol. 496 (2006) 723-38.
Marson L. and A.Z. Murphy. Identification of neural circuits involved in female sexual response: a dual virus and anterograde tracing study. Am J Physiol Regul Integr Comp Physiol. 2006 Feb 16; [Epub ahead of print].
Wang, X., R.J. Traub and A.Z. Murphy Systemic morphine produces a greater degree of analgesia in male versus female rats in a model of persistent pain. Am J Physiol Regul Integr Comp Physiol. 2006 Feb 23; [Epub ahead of print].
See more publications >>
Grant Support:
NIH/NIDA, NIH/NIAMS
Back to top
|
