[From inflammation to pain: experimental gene therapy].
Chronic pain is frequently associated with profound alterations of neuronal systems involved in pain processing and should be considered as a real disease state of the nervous system. Unfortunately, some forms of chronic pain remain difficult to be satisfactorily treated. In the search for new therapeutic strategies, the gene-based approaches are of potential interest as they offer the possibility to introduce a therapeutic protein into some relevant structures and to drive its continuous production in the near vicinity of targeted cells. Recently, these techniques have been experimented in several animal models of chronic pain, showing that transfer at the spinal level of some genes, in particular those of opioid precursors proopiomelanocortin or proenkephalin A, leading to the overproduction of products that they encode, attenuated persistent pain of both inflammatory and neuropathic origin. Thus, in polyarthritic rat, a model of chronic inflammatory pain, we demonstrated that herpes simplex virus vector mediated overexpression of proenkephalin A in primary sensory neurons at the lumbar level elicited both antihyperalgesic and anti-inflammatory activities. Apart from opioids, numerous other molecules involved in pain processing are of potential therapeutic interest for gene-based protocols. For instance, targeting some molecules involved in pain induction and perpetuation, such as proinflammatory cytokines, raises an interesting possibility to block the "development" of pain. The clinical application of these approaches remains to be established, and, presently, one of the main problems to be solved is the innocuity of virus-derived vectors. However, the experimental use of gene-based techniques might be particularly useful for the evaluation of the therapeutic interest of some recently identified molecules involved in pain processing and might finally lead to the development of new "classical" pharmacological tools.
Meunier
Alice
A
Inserm E0331, Inserm U.288, Douleurs et stress, Faculté de Médecine Pitié-Salpêtrière, 91, boulevard de l'Hôpital, 75634 Paris Cedex 13, France.
Braz
Joao
J
Cesselin
François
F
Hamon
Michel
M
Pohl
Michel
M
D000818:Animals; D001168:Arthritis / Q000150:complications / Q000503:physiopathology / Q000662:veterinary; D002908:Chronic Disease; D016207:Cytokines / Q000235:genetics / Q000494:pharmacology; D004195:Disease Models, Animal; D004745:Enkephalins / Q000494:pharmacology; D015316:Genetic Therapy / Q000639:trends*; D006801:Humans; D007249:Inflammation; D010146:Pain / Q000235:genetics*; D059408:Pain Management; D011498:Protein Precursors / Q000494:pharmacology; D051381:Rats
D016207:Cytokines; D004745:Enkephalins; D011498:Protein Precursors; C029992:proenkephalin