Central and peripheral expression of neurokinin-1 and neurokinin-3 receptor and substance P-encoding messenger RNAs: peripheral regulation during formalin-induced inflammation and lack of neurokinin receptor expression in primary afferent sensory neurons.

Abstract

The neurokinin-1 receptor and its tachykinin neuropeptide ligand substance P are associated with the mediation of nociception. Substance P released from primary afferent sensory neurons activates neurokinin receptors on both central and peripheral targets that mediate specific aspects of central sensitization and inflammatory function; however, an autoreceptor function for the neurokinin-1 receptor remains highly controversial. Activation of the neurokinin-1 receptor by substance P during chronic nociception increases neurokinin-1 receptor gene expression in the spinal cord. Similarly, neurokinin-3 receptors on peripheral or target tissues or neurons could play an important role in the sensitization of sensory neurons. Therefore, this study (i) mapped the steady-state levels of substance P-encoding preprotachykinin, neurokinin-1 and neurokinin-3 receptor messenger RNAs in central and peripheral tissues including sensory ganglia, and (ii) investigated whether formalin-evoked nociception altered the quantity or location of neurokinin-1 or neurokinin-3 receptor messenger RNAs in the sensory ganglia or inflamed peripheral targets for substance P. Solution hybridization-nuclease protection assays quantified neurokinin receptor messenger RNA levels in central and peripheral tissues from normal and formalin-inflamed rats. High concentrations of the neurokinin-1 receptor were found in whole brain, spinal cord, and peripheral target organs innervated by substance P-containing neurons. Measurable levels of neurokinin-3 receptor messenger RNA were found only in brain, spinal cord and urinary bladder. Results also show that neither neurokinin-1 nor neurokinin-3 receptor messenger RNAs were detectable in primary afferent sensory neurons in the dorsal root ganglia of normal or formalin-inflamed rats. Neurokinin-1 receptor messenger RNA levels were, however, significantly increased in hindpaw tissues inflamed by formalin for 6 h. These results indicate that the plasticity of neurokinin-1 receptor gene expression in non-neuronal peripheral cells could regulate sensitivity to substance P in a manner similar to that in the spinal cord dorsal horn. Altered neurokinin-1 receptor gene expression provides a useful marker of long-term nociceptive activation and may mediate peripheral mechanisms of hyperalgesia and cellular sensitization during inflammation. Importantly, inflammation does not induce a phenotypic change in afferent sensory neurons providing neurokinin receptor targets for the direct sensitization of these neurons by substance P.

• Authors: K E McCarson
• Journal: Neuroscience (Neuroscience) Vol. 93 Issue 1 Pg. 361-70 ( 1999) ISSN: 0306-4522 [Print] United States
• PMID: 10430499 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA Probes
• RNA, Messenger
• Receptors, Neurokinin-1
• Receptors, Neurokinin-3
• Formaldehyde
• Substance P
• Ribonucleases

Topics

• Animals
• Central Nervous System (metabolism, pathology)
• Formaldehyde (toxicity)
• In Situ Hybridization
• Male
• Neuritis (chemically induced, pathology)
• Neurons, Afferent (metabolism, pathology)
• Peripheral Nervous System (metabolism, pathology)
• Plasmids (drug effects, genetics)
• RNA Probes
• RNA, Messenger (biosynthesis)
• Rats
• Rats, Sprague-Dawley
• Receptors, Neurokinin-1 (biosynthesis)
• Receptors, Neurokinin-3 (biosynthesis)
• Ribonucleases
• Substance P (biosynthesis)
• Tissue Distribution
• Transcription, Genetic