Genetic deletion of pleiotrophin leads to disruption of spinal nociceptive transmission: evidence for pleiotrophin modulation of morphine-induced analgesia.
Pleiotrophin (PTN) is a growth factor that exhibits neurotrophic actions and is upregulated at sites of nerve injury. Upregulation of PTN levels in injured dorsal root ganglion correlates with decreased mechanical allodynia and faster recovery from Chronic Constriction Injury of the rat sciatic nerve. Despite the evidence pointing to a role of PTN in the development of chronic pain, the role of this neurotrophic factor in pain transmission has not been assessed in acute pain models. We have now studied the behaviour of PTN genetically deficient (PTN-/-) and wild type (PTN+/+) mice in the hot-plate and tail-immersion tests. We found that basal central pain responses do not differ between PTN-/- and PTN+/+ mice in the hot-plate test. Very interestingly, basal latencies to a tail flick were significantly increased in PTN-/- mice as assessed in the tail-immersion test. It was also aimed to evaluate morphine-induced analgesia in PTN-/- and PTN+/+ mice. We did not find differences among genotypes using a high dose of morphine (10 mg/kg) in the hot-plate test, reaching this dose the analgesia peak 25 min after injection (i.p.) and returning to almost basal values 125 min after injection. In contrast, we found that an intermediate dose of morphine (5 mg/kg) significantly delayed pain responses in PTN-/- mice compared to PTN+/+ mice in both the hot-plate and tail-immersion tests. The data strongly suggest that PTN is of critical importance for pain processing at the spinal level and, furthermore, that endogenous PTN modulates morphine-induced analgesic effects in mice.
Gramage
Esther
E
Laboratory of Pharmacology and Toxicology, Universidad San Pablo CEU, Urb. Montepríncipe, Madrid, Spain.
Herradon
Gonzalo
G
D000698:Analgesia; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000378:metabolism; D010147:Pain Measurement; D017450:Receptors, Opioid, mu / Q000502:physiology; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries; D013127:Spinal Nerves / Q000187:drug effects*; D013997:Time Factors
D000701:Analgesics, Opioid; D002352:Carrier Proteins; D016207:Cytokines; D017450:Receptors, Opioid, mu; C066845:pleiotrophin; D009020:Morphine