dynorphin-(1-32) and Pain

Animal models are useful to evaluate pharmacological therapies to alleviate joint pain. The present study characterized central neuropeptides modulation in the monoiodoacetate (MIA) rat model. Animals receiving a single 3mg MIA injection were euthanized at 3, 7, 14, 21 and 28 days post injection. Spinal cords were analyzed by liquid chromatography ion trap mass spectrometry. Up-regulations of the calcitonin gene-related peptide and substance P were observed starting on days 7 and 28 respectively, whereas big dynorphin(₁₋₃₂) content decreased significantly on day 14 in comparison to control animals (P<0.05). Preclinical drug evaluations using this model should be conducted between 7 and 21 days post injection when the lesions resemble most to human osteoarthritis.

Topics: Animals; Calcitonin Gene-Related Peptide; Chromatography, Liquid; Disease Models, Animal; Dynorphins; Enzyme Inhibitors; Humans; Iodoacetic Acid; Knee Joint; Male; Neuropeptides; Osteoarthritis; Pain; Rats; Rats, Sprague-Dawley; Spinal Cord; Substance P; Tandem Mass Spectrometry; Time Factors

The opioid peptide dynorphin1-32 (DYN1-32, 25 nmol) intrathecally administered causes, in the rat, an elevation of nociceptive threshold of longer duration than that of DYN A, as ascertained by vocalization test. Comparative findings obtained with tail flick test allow to differentiate antinociception from motor dysfunction. The breakdown of DYN A at spinal level is very rapid. The electrical stimulation of the tail associated to a restraint condition of the rat produces a significant increase of immunoreactive DYN in cervical, thoracic and lumbar segments of spinal cord, therefore indicating a correlative, if not causal, relationship between the spinal dynorphinergic system and aversive stimuli.

Topics: Analgesics; Animals; Dynorphins; Male; Pain; Rats; Rats, Inbred Strains; Sensory Thresholds; Spinal Cord; Synaptic Transmission