Lorne Mendell

Functional effects of neurotrophins in pain and segmental reflex pathways

Lorne Mendell
Distinguished Professor
PhD MIT

Viktor Arvonov, Research Assistant Professor
Xiaoquan (Tim) Shu – Research Assistant Professor Samuel Galoyan, Research Scientist
Sandra Garraway, Postdoctoral Fellow
Jeff Petruska, Postdoctoral Fellow
Alex Adler- Research Technician
Ying Lu - Graduate Student

The present focus of this laboratory is the physiology of neurotrophins, specifically their action in modifying well- delineated circuits in the intact and injured spinal cord, including sensory input and motor output.

We are investigating the effects of neurotrophins on nociceptors and nociception in rats. In previous work we determined that administration of the neurotrophin Nerve Growth Factor (NGF), known to be normally upregulated in skin during inflammation, produces hyperalgesia. At present we are studying the basis for the peripheral component of this hyperalgesia. We have determined that it involves sensitization of individual peripheral nociceptive afferent fibers. Our current evidence indicates that this sensitization includes both direct effects on the sensory afferents themselves as well as indirect effects mediated by immune-competent cells known as mast cells. The techniques employed in these experiments include electrophysiological recording from individual sensory neurons both in vivo and in an in vitro skin nerve preparation as well as whole cell patch clamp recording from individual dorsal root ganglion cells in dissociated cell culture.

A second focus in this laboratory is the action of neurotrophins such as NT-3 and BDNF on spinal reflexes and pathways in the neonatal rat. We have found that neurotrophins can influence transmission acutely and we are studying mechanisms by which these interactions take place, specifically the role of NMDA- receptors. One possible implication of these studies is developmental since we have found that neutralization of neurotrophins or provision of additional neurotrophins affects the postnatal development of these reflex connections. A second possible implication is for recovery of synaptic function after neuronal injury since we believe that neurotrophins may play an important role in reestablishment of functional synaptic connections. A third implication is the role of neurotrophins in modifying spinal pain circuits since intrathecal BDNF is now known to cause hyperalgesia. These studies involve intracellular recording from spinal neurons in the in vitro spinal cord as well as in vivo.

Recent representative publications:

Mendell, L.M. (1995) Neurotrophic factors and the specification of neural function. The Neuroscientist. 1: 26-34.

Mendell, L.M. (1996) Neurotrophins and sensory neurons: role in development, maintenance and injury. A thematic summary. Phil.
Trans. R. Soc. Lond. B. 351: 463- 467.

Seebach, B.S. and Mendell, L.M. (1996) Maturation in properties of motoneurons and segmental input in the neonatal rat. J.
Neurophysiol. 76: 3875- 3885.

Rueff, A. and Mendell, L.M. (1996) Nerve growth factor and NT-5 induce increased thermal sensitivity of cutaneous nociceptors in vitro.
J. Neurophysiol. 76: 3593- 3596.

Munson, J.B., Johnson, R.D., Mendell, L.M. and Gordon, T. (1997) Fast-to-slow conversion following chronic low- frequency activation of
medial gastrocnemius muscle in cats. II. Motoneuron Properties. J. Neurophysiol. 77: 2605- 2615.

Tonra, J.R. and Mendell, L.M. (1998) The effects of postnatal anti-NGF on the development of CGRP-IR neurons. J. Comp. Neurol. 392:
489- 498.

Shu, X-Q, Lllinas, A. and Mendell, L.M. (1999) Effects of trkB and trkC neurotrophin receptor agonists on thermal nociception: a
behavioural and electrophysiological study. Pain 80: 463- 470.

Seebach, B.S., Arvanov, V. and Mendell, L.M. (1999) Neurotrophin influence on the development of segmental reflexes in the rat. J.
Neurophysiol. 81: 2398- 2405

Munson, J.B., Johnson, R.B. and Mendell, L.M. (1999) Neurotrophin action on the recovery of the monosynaptic reflex after peripheral
axotomy in the cat. J. Neurosci. 19: 3162-3170.

Shu, X.-Q. and Mendell L.M. (1999) Neurotrophins and Hyperalgesia. Proceedings of the National Academy of Sciences 96: 7693-7696

Mendell, L.M., Albers, K.M. and Davis, B.M. (1999) Neurotrophins, Nociceptors and Pain. Microscopy Research and Technique. 45:
252-261.