- Email: [email protected]
Neurones activity in spinal dorsal horn of rats after sciatic nerve section
MECHANICAL ALLODYNIA IS NOT MEDIATED BY A CENTRAL PRESYNAPTIC INTERACTION OF Al%MECHANOCEPTNE AND NOCICEI’TIVE C-AFFERENTS
NEURONES ACTIVITY IN SPINAL DORSAL HORN OF RATS AFTER SCIATIC NERVE SECTION
DYNAMIC
G.
V. K. Reshetnyak Institute of General Patholoa and Pathophysiology, Russian Academy ofMedical Sciences Moscow, Russia.
Was&, R. Baron’. W. JPnig*
‘Khikfiir
Neurologie, ‘Physiologisches Instifur, Chrrstiun-Albrechtr-
Universitiir zu Kie/, Kid
Germanv
Using the capsaicm (CAP) m humans II was shown that hghr mechanical stimulation within the area of secondary mechamcal allodynia induces vasodilauon measured by laser Doppler flowmetry It was concluded that low threshold AR-mechanoceptive fibers gain access to nocicepuve afferent neurons at a central presynaptic level wa mterneurons and that the vasodilation 1s mediated by dorsal root reflex activity conducted antidromically m nociceptive C-fibers (Cervero & Laird, Pain 1996). We refuted tlus idea using the following experimental protocol before and after intracutaneous CAP injection (IO 1.11,0.9%): Ten mm apart from a laser Doppler the skin was stimulated for I min (I) by movmg a cotton swab and (2) by electrically stimulating the afferents transdermally. lncreasmg atlmulu mtensmes were applied (0.3 4 mA. 46 Hz, pulse duratlon 0.2 ms) After CAP Injection, hght mechanical stimulation ehuted a burmng pamful sensation regularly paralleled by movement artefacts at the laser signal. A characteristic antidronuc vasodilation was never observed. Electrical stimulation at intensities that were not pamful before CAP injection (A&stimulation)was now able to ehcit a burning painful sensation. No change m blood flow was detected. When the stimulu intensities were mcreased reaching levels that were also pamful before CAP treatment (C-fiber stimulation) an axon reflex vasodilatationcould be Induced (typuzal time course). In conclusion, electrical stimulation of A!&fibers in allodynic skm does not induce antidromic vasodilation. Therefore, the idea popagated by Cervero & Laird lacks experimental basis. It is much more likely that under pathophysiological conditions activity in A&fibers may activate spmal nociceptive second-order neurons.
The aim of this research was to study background and evoked neuronal activity in spinal cord dorsal horn in rats with and without neurogenic pain syndrome after sciatic nerve section. The development of pain syndrome determined in appearance of autonomies on the limb with cutting nerve. It was shown that in rats with neurogenic pain unlike the rats without pain in the dorsal horn at the side of the injured limb an increase in the background activity of single neurons, an appearance of spontaneous paroxismal burst discharges and prolonged after discharges, were observed. The results show that in rats with neurogenic pain in the dorsal horn neurones of the damaged limb side is formed a generator of pathologically enhanced excitation which represent aggregates of hyperactive neurones with attenuated inhibitory properties capable of developing a self-sustained activity and producing an abnormal flow of impulses.
027 VASCULAR
ENDOTHELIAL
AND RECEPTORS INVOLVED AND LYMPHANGIOGENESIS
GROWTH
FACTORS
IN ANGIOGENESIS
Kari Alitalo and collaborators Molecular/Cancer Biology Laboratory, Haartman Institute and Department of Biomedicine, Universiw of Helsinki VEGF uses the Flt-I (VEGFR-1)
and Flk-I/KDR (VEGFRfor signal transduction in endothelial cells, whereas VEGF-B and PIGF use only VEGFR-I (Olofsson et al., submitted). Targeted mutagenesis shows that Flt4 (VEGFR3) has an early vascular function (Dumont et al., submitted for publication), but becomes restricted mainly to lymphatic endothelia during further development. The Flt4 ligand, VEGF-C is synthesized as a precursor protein requiring proteolytic processing for activation. Transgenic mice overexpressing VEGF-C develop a hyperplastic lymphatic vessel network and recombinant mature VEGF-C induced a rather selective growth of lymphatic vessels in mature CAM. However, proteolytically processed VEGF-C was also capable of stimulating VEGFR-2 and was weakly angiogenic. VEGF-C also induced vascular permeability, but its point mutant, which activated only VEGFR-3 did not. VEGF-D/FIGF is closely related to VEGF-C, proteolytically processed and binds to the same receptors. Thus, VEGF and VEGF-C appear to be relatively specific angiogenic and lymphangiogenic growth factors, respectively. 2) receptors
168
NEURONES ACTIVITY IN SPINAL DORSAL HORN OF RATS AFTER SCIATIC NERVE SECTION
DYNAMIC
G.
V. K. Reshetnyak Institute of General Patholoa and Pathophysiology, Russian Academy ofMedical Sciences Moscow, Russia.
Was&, R. Baron’. W. JPnig*
‘Khikfiir
Neurologie, ‘Physiologisches Instifur, Chrrstiun-Albrechtr-
Universitiir zu Kie/, Kid
Germanv
Using the capsaicm (CAP) m humans II was shown that hghr mechanical stimulation within the area of secondary mechamcal allodynia induces vasodilauon measured by laser Doppler flowmetry It was concluded that low threshold AR-mechanoceptive fibers gain access to nocicepuve afferent neurons at a central presynaptic level wa mterneurons and that the vasodilation 1s mediated by dorsal root reflex activity conducted antidromically m nociceptive C-fibers (Cervero & Laird, Pain 1996). We refuted tlus idea using the following experimental protocol before and after intracutaneous CAP injection (IO 1.11,0.9%): Ten mm apart from a laser Doppler the skin was stimulated for I min (I) by movmg a cotton swab and (2) by electrically stimulating the afferents transdermally. lncreasmg atlmulu mtensmes were applied (0.3 4 mA. 46 Hz, pulse duratlon 0.2 ms) After CAP Injection, hght mechanical stimulation ehuted a burmng pamful sensation regularly paralleled by movement artefacts at the laser signal. A characteristic antidronuc vasodilation was never observed. Electrical stimulation at intensities that were not pamful before CAP injection (A&stimulation)was now able to ehcit a burning painful sensation. No change m blood flow was detected. When the stimulu intensities were mcreased reaching levels that were also pamful before CAP treatment (C-fiber stimulation) an axon reflex vasodilatationcould be Induced (typuzal time course). In conclusion, electrical stimulation of A!&fibers in allodynic skm does not induce antidromic vasodilation. Therefore, the idea popagated by Cervero & Laird lacks experimental basis. It is much more likely that under pathophysiological conditions activity in A&fibers may activate spmal nociceptive second-order neurons.
The aim of this research was to study background and evoked neuronal activity in spinal cord dorsal horn in rats with and without neurogenic pain syndrome after sciatic nerve section. The development of pain syndrome determined in appearance of autonomies on the limb with cutting nerve. It was shown that in rats with neurogenic pain unlike the rats without pain in the dorsal horn at the side of the injured limb an increase in the background activity of single neurons, an appearance of spontaneous paroxismal burst discharges and prolonged after discharges, were observed. The results show that in rats with neurogenic pain in the dorsal horn neurones of the damaged limb side is formed a generator of pathologically enhanced excitation which represent aggregates of hyperactive neurones with attenuated inhibitory properties capable of developing a self-sustained activity and producing an abnormal flow of impulses.
027 VASCULAR
ENDOTHELIAL
AND RECEPTORS INVOLVED AND LYMPHANGIOGENESIS
GROWTH
FACTORS
IN ANGIOGENESIS
Kari Alitalo and collaborators Molecular/Cancer Biology Laboratory, Haartman Institute and Department of Biomedicine, Universiw of Helsinki VEGF uses the Flt-I (VEGFR-1)
and Flk-I/KDR (VEGFRfor signal transduction in endothelial cells, whereas VEGF-B and PIGF use only VEGFR-I (Olofsson et al., submitted). Targeted mutagenesis shows that Flt4 (VEGFR3) has an early vascular function (Dumont et al., submitted for publication), but becomes restricted mainly to lymphatic endothelia during further development. The Flt4 ligand, VEGF-C is synthesized as a precursor protein requiring proteolytic processing for activation. Transgenic mice overexpressing VEGF-C develop a hyperplastic lymphatic vessel network and recombinant mature VEGF-C induced a rather selective growth of lymphatic vessels in mature CAM. However, proteolytically processed VEGF-C was also capable of stimulating VEGFR-2 and was weakly angiogenic. VEGF-C also induced vascular permeability, but its point mutant, which activated only VEGFR-3 did not. VEGF-D/FIGF is closely related to VEGF-C, proteolytically processed and binds to the same receptors. Thus, VEGF and VEGF-C appear to be relatively specific angiogenic and lymphangiogenic growth factors, respectively. 2) receptors
168