Effects Of Intrathecal BAM22 On Nociceptive Responses And Expression Of C-Fos Protein In The Rat Spinal Dorsal Horn

Bovine adrenal medulla 22 (BAM22), a cleaved product of proenkepha-lin A, is found in the central nervous system including the cerebral cortex, caudate putamen, hippocampus, hypothalamus, periaqueductal gray, midbrain and spinal cord. BAM22 binds to μ-, δ- and K-opioid receptors with a high affinity and also potently activates the sensory neuron-specific receptor (SNSR), a novel receptor that is uniquely distributed in small-diameter neurons in the dorsal root ganglia (DRG) and trigeminal ganglia. The fact that BAM22 seems to be only endogenous ligand that activates SNSR makes it very interesting and important to investigate BAM22. The present study examined the effects of BAM22 and BAM8-22 on nociceptive responses in naive animals and the animals with injury at the systemic and cellular levels using behavioral assays and immunocytochemistry.The study demonstrated that intrathecal (i.t.) BAM22 decreased nocifensive behavior in the first and second phases of the formalin test, and increased the tail-withdrawal (TW) latency. Furthermore, these results were associated with decreases of formalin-induced expressions of c-fos-like immunoreactivity in laminae I-II, HI-IV and V-VI of the spinal cord. The BAM22-induced behavior and neuronal responses were significantly attenuated, but not completely abolished by intraperitoneal (i.p.) the opioid receptor antagonist naloxone at maximally effective doses (1-10 mg/kg). The study also demonstrated that intrathecal BAM8-22 inhibited nocifensive behavior in the second phase of the formalin test.These results indicate that BAM22 suppresses nociceptive processing at the spinal level via opioid and non-opioid mechanisms. This is the first study to demonstrate that SNSR is involved in pain modulation.