Our laboratory has focused on studying the influence of the brain stem on the sensation of pain. Pain is modulated at several anatomical sites, including the spinal cord and the rostral ventromedial medulla (RVM) in the brainstem. Physiological studies suggest that RVM neurons containing inhibitory neurotransmitters have axons that descend to the spinal cord, inhibiting spinal neurons that relay pain to the brain. However, in addition, there is evidence that excitatory neurons in the same region can facilitate pain.
The present focus of our work is the neuroanatomical circuitry underlying neuropathic pain. Pain can arise from damage (or the threat of damage) to the body. However, pain can also result from prior damage to a nerve; the resulting pain occurs without any threat of damage to the body and is referred to as neuropathic pain. Our laboratory recently discovered that over 20% of all neurons in the RVM are lost in response to damage to a peripheral nerve. However, this cell loss could be blocked completely by a drug (tauroursodeoxycholic acid, or TUDCA) that inhibits programmed cell death, or apoptosis.
Neuronal loss such as we observed in the RVM appears to be unprecedented: there are no direct synaptic connections between the RVM and the peripheral nerve that was lesioned, nor even between the peripheral nerve and neurons that project their axons to the RVM. Thus we currently are investigating the mechanism underlying this loss of RVM neurons, examining whether such “long-distance” cell loss might be occurring in response to other insults, trying to assess whether a specific population of RVM neurons (e.g. antinociceptive neurons) are lost after peripheral nerve damage, and attempting to determine whether TUDCA could be useful for preventing neuropathic pain in humans.
Our laboratory also collaborates with other researchers to examine the anatomical basis of sex differences in pain and analgesia. These studies have focused in particular on the interactions of sex steroids and opiate receptors.
In addition to our work on pain, we have also promoted methods for multi-color fluorescence microscopy as a research tool, and are presently developing optical microscopic methods related to confocal microscopy, digital deconvolution and optical super-resolution. The latter method allows the light microscope to attain resolution previously possible only with the electron microscope.
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
Leong ML, Speltz R, Wessendorf M. Effects of chronic constriction injury and spared nerve injury, two models of neuropathic pain, on the numbers of neurons and glia in the rostral ventromedial medulla. Neurosci Lett. 2016 Feb 6;617:82-87. [Epub ahead of print]
Leong ML. Gu M. Speltz-Paiz R. Stahura EI. Mottey N. Steer CJ. Wessendorf M. “Neuronal loss in the rostral ventromedial medulla in a rat model of neuropathic pain.”, Journal of Neuroscience 31(47):17028-39, 2011
Liu NJ. Chakrabarti S. Schnell S. Wessendorf M. Gintzler AR. “Spinal synthesis of estrogen and concomitant signaling by membrane estrogen receptors regulate spinal kappa- and mu-opioid receptor heterodimerization and female-specific spinal morphine antinociception.”, Journal of Neuroscience 31(33):11836-45, 2011
Arora D, Hearing M, Haluk DM, Mirkovic K, Fajardo-Serrano A, Wessendorf MW, Watanabe M, Luján R, Wickman K. Acute cocaine exposure weakens GABA(B) receptor-dependent G-protein-gated inwardly rectifying K+ signaling in dopamine neurons of the ventral tegmental area. J Neurosci. 2011 Aug 24;31(34):12251-7.
Schnell SA, Wessendorf MW. Lack of evidence for the mu-opioid receptor splice variant MOR1C in rats. J Comp Neurol. 2009 Dec 1;517(4):452-8.
Schnell SA, Wessendorf MW. Coexpression of the mu-opioid receptor splice variant MOR(1C) and the vesicular glutamate transporter 2 (VGLUT2) in rat central nervous system. J Comp Neurol. 2008 Mar 31
Marinelli S, Connor M, Schnell SA, Christie MJ, Wessendorf MW, Vaughan CW. delta-opioid receptor-mediated actions on rostral ventromedial medulla neurons. Neuroscience. 2005;132(2):239-44.
Marinelli S, Schnell SA, Hack SP, Christie MJ, Wessendorf MW, Vaughan CW. Serotonergic and nonserotonergic dorsal raphe neurons are pharmacologically and electrophysiologically heterogeneous. J Neurophysiol. 2004 Dec;92(6):3532-7.
Wessendorf MW, Wang H, Schnell SA. Statistical methods for in situ hybridization: identification of autoradiographically labelled cells and structures. J Microsc. 2004 Jul;215(Pt 1):50-61.
Schnell SA, Wessendorf MW. Expression of MOR1C-like mu-opioid receptor mRNA in rats. J Comp Neurol. 2004 May 24;473(2):213-32.
Brelje TC, Wessendorf MW, Sorenson RL. Multicolor laser scanning confocal immunofluorescence microscopy: practical application and limitations. Methods Cell Biol. 2002;70:165-244.
Marinelli S, Vaughan CW, Schnell SA, Wessendorf MW, Christie MJ. Rostral ventromedial medulla neurons that project to the spinal cord express multiple opioid receptor phenotypes. J Neurosci. 2002 Dec 15;22(24):10847-55.
Former Graduate Students:
Ming Gu (Ph.D. 2007, Neuroscience, University of Minnesota).
Heather Leong (Ph.D. 2011, Neuroscience, University of Minnesota).
Sara Tallaksen-Greene (Ph.D.). Currently at the Department of Neurology, Univ. of Michigan, Ann Arbor
Wei Wu (Ph.D.). Currently at the Howard Hughes Research Institute, University of California-San Diego, La Jolla, CA