Tuberoinfundibular peptide of 39 residues (TIP39) modulates neuropathic pain

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NIMH	NEURO/BEHAV/SENSYS-9

Authors

• E Dimitrov
• Y Kim
• T Usdin

Abstract

Neuropathic pain, manifest as burning or tingling and ache, has diverse causes and is often devastating to affected individuals. Available drugs have narrow therapeutic indices and multiple side effects. Manipulation of endogenous modulatory systems may present additional treatment approaches. We recently found that TIP39, via its receptor the PTH2R, increases acute nociception, acting mainly at the supraspinal level. TIP39 is produced by posterior thalamic and lateral brainstem neurons with limbic- and pain-associated region projections. Here we investigated TIP39 involvement in neuropathic pain, comparing thermal and tactile sensitivity between WT and PTH2R-KO mice following partial sciatic nerve ligation (PNL). Tactile thresholds were the same before surgery and similar hypersensitivity developed. Starting around the 10th postsurgical day mechanical hypersensitivity of KO-mice decreased. The difference between the tactile thresholds of WT- and KO-mice further increased over time. KO-mice did not develop thermal hypersensitivity after PNL, while WT did. In WT, TIP39 mRNA increased in the MPL following PNL. Thus, TIP39 exerts a pronociceptive function in neuropathic pain. Previous experiments suggest TIP39 signaling modulates amygdalar endocannabinoid activity. Ongoing experiments address whether this is the locus of TIP39’s contribution to neuropathic pain, and whether PTH2R block has therapeutic promise, based on anatomically discrete endocannabinoid modulation.

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