MEDICAL HYPOTHESES AND RESEARCH
VOL. 1, No. 1, January 2005


G. T. Whiteside, et al. [2005] Med Hypotheses Res 2: 275-282.

Ablation of a Population of Neurons in the Dorsal
Horn of the Spinal Cord is Insufficient to Induce
Sprouting of Touch Responsive Myelinated Afferents
into the Innervation Territory of Pain Sensitive
Unmyelinated Afferents


Garth T. Whiteside*, Morgan E. Woods, Michelle S. Pearson, James
D. Pomonis, Paul I. Turchin and Katharine Walker

Purdue Pharma, Discovery Research, 6 Cedar Brook Drive, Cranbury, New Jersey 08512,
USA


Abstract. It has been proposed that the sprouting of touch responsive Aβ-fibers into
the innervation territory of pain sensitive C-fibers in the spinal cord contributes to pain
behaviors following peripheral nerve injury. The stimulus for Aβ sprouting is unclear, but
it has been proposed that the death of dorsal horn neurons may result in “vacant
synapses” that could act as a sufficient stimulus to induce sprouting. In order to test this
hypothesis, we have investigated whether selectively ablating a population of cells in
laminas I and II, in the absence of peripheral nerve injury, would induce sprouting of Aβ-
fibers as identified using the selective transganglionic tracer, cholera toxin-β. We
demonstrate that intrathecal injection of a substance P and saporin conjugate caused a
statistically significant reduction of neurokinin 1 immunostaining in the rat spinal cord.
However, this ablation of dorsal horn neurons did not result in the presence of cholera
toxin-β in the dorsal part of lamina II, as was observed following axotomy of the sciatic
nerve. These data suggest that the death of dorsal horn neurons, in the absence of
peripheral nerve damage, does not necessarily induce sprouting of Aβ-fibers into lamina II.

*Address all correspondence to: Dr. Garth T. Whiteside, Pharmacology, Purdue Pharma
LP, 6 Cedar Brook Drive, Cranbury, NJ 08512, USA.
Phone: 609-409-5778. Fax: 609-409-6922. E-Mail:
garth.whiteside@pharma.com


Full Text [PDF]