Neuropeptide FF in the lateral spinal and lateral cervical nuclei: Evidence of contacts on spinothalamic neurons

Neuropeptide FF (NPFF, F8Famide) is best known for its modulating effect on opioid analgesia and morphine tolerance. However, the exact mode of action of NPFF in sensory transmission is not known. We compared the distribution of NPFF-immunoreactive (ir) fibers and terminal-like thickenings with the retrograde, tracer-filled spinothalamic (ST) neurons in the lateral spinal nucleus (LSN) and lateral cervical nucleus (LCN) of rat, areas where NPFF-containing nerve terminals are abundant. We injected fluorescent latex microspheres into the ventroposterolateral thalamic nucleus and more medial thalamic nuclei, which are innervated by ST neurons. We found NPFF-ir terminal-like thickenings and fibers apposing the tracer-filled neurons in the LSN and LCN. ST neurons filled with the retrograde tracer making contacts with NPFF-ir terminal-like thickenings, were found to terminate not only in the ventroposterolateral thalamic nucleus but also in more medial thalamic nuclei. The highest number of tracer-filled ST neurons having NPFF-ir terminal-like thickenings and fibers in apposition were found at the cervical level. Our results suggest that NPFF-containing systems in the spinal cord of rat are not limited to the substantia gelatinosa, and the sensory functions of NPFF may be mediated at least partly through the modulation of the ST system. NPFF-ir contacts in the LSN and LCN might play an important role in the somatic sensory transmission system. This study shows evidence for the first time that the spinal NPFF-containing system may be involved in mechanisms that control sensory input to the supraspinal levels.