Evidence for biological effects of exogenous LPA on rat primary afferent and spinal cord neurons.
There is growing behavioural evidence that the phospholipid growth factor lysophosphatidic acid (LPA) modulates nociceptive responses in vivo. The present study investigated further the effects of LPA on peripheral nociceptive processing. Effects of intraplantar injection of LPA on ongoing and peripheral mechanically evoked responses of spinal neurons were studied in vivo. In addition, LPA-evoked responses of adult rat dorsal root ganglion (DRG) neurons were studied with calcium imaging. To determine whether LPA may also act at the level of the spinal cord, LPA receptor G-protein coupling in lumbar spinal cord sections was studied with in vitro autoradiography of guanylyl 5'-[g-[(35)S]thio]triphosphate ([(35)S]GTPgammaS) binding. Intraplantar injection of LPA (5 microg/5 microl) significantly increased the duration (P<0.001) and frequency of spinal neuronal firing (P<0.01), compared to vehicle. Intraplantar injection of LPA (1 microg/5 microl) did not significantly alter innocuous and noxious mechanically evoked responses of spinal neurons, but a higher dose of LPA (5 microg) significantly (P<0.05) attenuated mechanically evoked responses of spinal neurons. Calcium imaging studies demonstrated that LPA (0.001-3 microM) increases intracellular calcium concentration in adult DRG neurons, suggesting that LPA can produce direct effects on. Incubation of spinal cord sections with LPA (1 microM) significantly (P<0.001) increased [(35)S]GTPgammaS binding in the superficial laminae of the dorsal horn of the spinal cord, suggesting that LPA may also have biological effects at this level. These data provide further evidence that exogenous LPA can modulate nociceptive processing and suggest that this may be mediated by a direct effect on primary afferent nociceptors.
Elmes
Steven J R
SJ
Institute of Neuroscience, School of Biomedical Sciences, E Floor, Medical School, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, United Kingdom. mbxsjre@nottingham.ac.uk
Millns
Paul J
PJ
Smart
Darren
D
Kendall
David A
DA
Chapman
Victoria
V
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000344:Afferent Pathways / Q000187:drug effects*; D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005727:Ganglia, Spinal / Q000166:cytology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects*; D010147:Pain Measurement / Q000379:methods; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013116:Spinal Cord / Q000166:cytology*; D018709:Statistics, Nonparametric; D013460:Sulfur Isotopes / Q000493:pharmacokinetics
D008246:Lysophospholipids; D009294:Narcotics; D013460:Sulfur Isotopes; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D011189:Potassium Chloride; D009020:Morphine; C032881:lysophosphatidic acid; D002118:Calcium