Dual localization of neuropeptide FF receptors in the rat dorsal horn

Although neuropeptide FF (NPFF) is generally considered an antiopioid, its intrathecal administration produces analgesia. In the present study, the st able analog 1DMe ([D.Tyr(1),(NMe)Phe(3)]neuropeptide FF) was used in quanti tative autoradiographic experiments in combination with surgical and chemic al lesions to precisely localize NPFF receptors in the rat spinal cord. Lig ation of lumbar dorsal spinal roots revealed the presence of NPFF receptors in dorsal root fibers and it induced a significant accumulation of [I-125] 1DMe-specific binding on the side peripheral to the ligature, demonstrating that a population of NPFF receptors is synthesized in dorsal root ganglia and migrates anterogradely towards primary afferent nerve endings. Complete midthoracic spinal cord transection failed to modify the [I-125]1DMe label ing density in the dorsal horn, indicating that NPFF receptors are not loca ted on the descending fiber terminals. In contrast, unilateral microinjecti ons of kainic acid into the dorsal horn dramatically reduced [I-125]1DMe-sp ecific binding in the superficial layers, revealing localization of a popul ation of NPFF receptors on the spinal intrinsic neurons. NPFF receptor bind ing was not modified during the development of spinal opioid tolerance. The pre- and postsynaptic localization of spinal NPFF receptors provide furthe r support for heterogeneity in the pain modulation by NPFF and related agon ists. Synapse 35:45-52, 2000. (C) 2000 Wiley-Liss, Inc.