VIP and PACAP in pain and inflammation.

In a recent TiPS article1xVIP and PACAP: very important in pain?. Dickinson, T. and Fleetwood-Walker, S.M. Trends Pharmacol. Sci. 1999; 20: 324–329Abstract | Full Text | Full Text PDF | PubMed | Scopus (100)See all References1, Dickinson and Fleetwood-Walker make a solid case for an important role for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) in the perception of pain. This view is based on the effects of selective agonists and antagonists of receptors for the two neuropeptides on electrophysiological activity of dorsal horn neurones in normal and neuropathic rats2xThe role of VIP/PACAP receptor subtypes in spinal somato-sensory processing in rats with an experimental peripheral mononeuropathy. Dickinson, T. et al. Neuropharmacology. 1999; 38: 167–180Crossref | PubMed | Scopus (61)See all References2, and on the upregulation of VIP and PACAP and some of their receptors following peripheral nerve injury.The authors’ conclusion is justified by the data presented and reviewed. However, because pain is often linked with inflammation in the minds of many, it might be assumed that VIP and PACAP generally promote inflammation. In reality, a large body of evidence from different experimental models suggests that VIP, and in many instances also PACAP, can prevent or suppress tissue injury and inflammation. Such evidence (summarized in Ref. 3xAntiinflammatory actions of VIP in the lungs and airways. Said, S.I. : 345–361See all ReferencesRef. 3) includes: (1) prevention of acute high-permeability pulmonary oedema caused by oxidant stress or glutamate; (2) attenuation of bronchoconstriction and airway inflammation induced by capsaicin, which releases the proinflammatory sensory neuropeptide tachykinins; (3) protection of CNS neurones against death induced by a variety of insults4xActivity-dependent neurotrophic factor: structure–activity relationships of femtomolar-acting peptides. Brenneman, D.E. et al. J. Pharmacol. Exp. Ther. 1998; 285: 619–627PubMedSee all References, 5xGlutamate toxicity in the lung and neuronal cells: prevention or attenuation by VIP and PACAP. Said, S.I. et al. Ann. New York Acad. Sci. 1998; 865: 226–237Crossref | PubMed | Scopus (42)See all References; and (4) inhibition of the production of tumour necrosis factor α and other inflammatory cytokines by lipopolysaccharide-stimulated macrophages6xVasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) protect mice from lethal endotoxemia through the inhibition of TNF-α and IL-6. Delgado, M. et al. J. Immunol. 1999; 162: 1200–1205PubMedSee all References6.The upregulation of VIP or PACAP, and of their receptors, elicited by acute injury or axotomy7xGalanin and vasoactive intestinal peptide messenger RNAs increase following axotomy of adult sympathetic neruons. Mohney, R.P. et al. J. Neurobiol. 1994; 25: 108–118Crossref | PubMedSee all References7, which is an example of messenger plasticity8xMessenger plasticity in primary sensory neurons following axotomy and its functional implications. Hokfelt, T. et al. Trends Neurosci. 1994; 17: 22–30Abstract | Full Text PDF | PubMed | Scopus (609)See all References8, might represent adaptive responses designed to modulate the inflammatory reaction, rather than to help bring it about9xVIP and messenger plasticity. Said, S.I. Trends Neurosci. 1994; 17: 339Abstract | Full Text PDF | PubMed | Scopus (2)See all References9.Therefore, the role of VIP or PACAP in the genesis and alleviation of pain and inflammation appears to be complex and its full clarification awaits further exploration.