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Tuberoinfundibular peptide of 39 residues decreases pain-related affective behavior

Tuberoinfundibular peptide of 39 residues (TIP39) is a recently identified parathyroid hormone 2 receptor ligand. Their CNS distributions suggest potential involvement in neuroendocrine, limbic and sensory processing functions. Herein we investigate the analgesic and antinociceptive actions of brain delivery of TIP39 in adult male rats. Intracerebroventricular (i.c.v.) TIP39 did not change hot-plate paw withdrawal latency or formalin test behavioral responses. TIP39 partially reversed tactile withdrawal hypersensitivity following carageenan administration. In the place/escape avoidance paradigm (PEAP), which evaluates affective components of responses to noxious stimuli by presenting a choice between a naturally preferred environment paired with stimulation of a carrageenan sensitized paw and a less preferred environment paired with stimulation of a less sensitive paw, TIP39 decreased the apparent aversiveness of sensitive paw stimulation. Because acute sensory thresholds were unaffected by TIP39, and the effects of i.c.v. TIP39 were opposite in direction from previously described effects of intrathecal TIP39, this suggests that TIP39 may modulate an affective component of nociception within the brain.