Editorial [ Pain Guest Editors: Robert W. Gereau IV & Ferdinando Nicoletti ]

Although morphine is still the gold-standard for the treatment of pathological pain, the increasing knowledge of the mechanisms that regulate pain threshold breaks the ground for the development of new potent and safe analgesic drugs. Hopefully, these drugs will relieve some forms of pain that are partially resistant to opiates, such as neuropathic pain. This issue of Current Neuropharmacology includes a series of excellent reviews that summarize the current knowledge and the most exciting perspectives on the neurobiology of pain. The opening review by Dr. Marchettini and collaborators is a nice clinical classification of peripheral neuropathies, which are a major source of neuropathic pain. If present, pain associated with peripheral neuropathies is extremely disabling, and its treatment is one of the major challenges in neuroscience. The two following reviews by Dr. Story and Dr. Mc Naughton’s group focus on the role of Trp channels in heat sensation and inflammatory pain. One of these channels, named TrpV1, is expressed by neurons of dorsal root ganglia, and responds to heat, protons, inflammatory mediators, and capsaicin. An increased sensitivity of the TrpV1 channel is central to the pathophysiology of heat hyperalgesia in inflammatory pain. The review by the group of Dr. Negri and Dr. Melchiorri describes the role of prokineticins and their receptors in the modulation of pain. Prokineticins are the mammalian homologs of Bv8, a small protein extracted from the frog skin that behaves as a potent hyperalgesic agent. The regulation of pain moves from the periphery to the CNS in the review by Dr. Tao and Dr. Johns, which describes the role of PDZ-domain-containing proteins associated with NMDA receptors in persistent pain. The review by the group of Dr. Maione and Dr. Rossi explores the complex interaction between metabotropic glutamate receptors and cannabinoid receptors in the periaqueductal grey, a region of the brainstem that is critical for the regulation of pain threshold. These two classes of receptors are considered as potential targets for novel analgesic drugs. Along this line, the review by Dr. Chiechio and collaborators describes the mechanism of action of Lacetylcarnitine, a drug that is currently used for the treatment of neuropathic pain. L-Acetylcarnitine up-regulates the expression of a particular metabotropic glutamate receptor subtype, the mGlu2 receptor, which inhibits neurotransmission at the synapse between primary afferent pathways and neurons in the dorsal horns of the spinal cord. Finally, the elegant review by Dr. Manzanares, Dr. Julian, and Dr. Carrascosa describes the multifaceted role of the cannabinoid system in pain transmission, and the potential therapeutic implications for the management of acute and chronic pain. Taken together, the articles included in the issue offer an original view of the molecular and transsynaptic mechanisms underlying inflammatory and neuropathic pain, and are particularly helpful for basic scientists and clinicians interested in the neuropharmacology of pain.