A- and C-fiber evoked ventral root potential (VRP) responses have been examined in isolated spinal cord preparations maintained in vitro that were taken from young rats in which behavioral hyperalgesia (thermal and mechanical) was induced following UV irradiation of one hindpaw. Evoked VRPs were compared with those in naive untreated animals. The duration of both the A- and C-fiber evoked VRP was significantly increased in UV-treated animals. The amplitude of the summated VRP evoked by repeated low-frequency (1.0–5.0 Hz) C-fiber stimulation, a measure of windup, was significantly greater in UV-treated animals. In UV-treated animals, repeated low-frequency (1.0–5.0 Hz) stimulation of A-fiber inputs to the spinal cord also evoked a significant summated VRP, which was not observed in spinal cords from untreated animals. In naive animals the prolonged VRP evoked following single shock C-fiber stimulation was significantly antagonized by the NMDA receptor antagonist D-AP5 and the NK2 receptor antagonist MEN, 10376 but not by the NK1 receptor antagonists CP-96,345 or RP,67580. Summated VRPs evoked by repeated C-fiber stimulation in naive animals were significantly antagonized only by D-AP5. In hyperalgesic animals the prolonged VRP evoked by C-fiber stimulation was significantly reduced by NK1, NK2, and NMDA antagonists. The summated VRP was also significantly reduced by these antagonists. In both untreated and UV- irradiated animals the single shock evoked A-fiber ventral root response was significantly antagonized only by D-AP5. However, the summated VRP evoked by repeated A-fiber stimulation in UV-treated animals was also significantly reduced by NMDA, NK1, and NK2 receptor antagonists. The present study has demonstrated enhanced A- and C-fiber evoked responses in the rat spinal cord in vitro following induction of a peripheral injury by UV irradiation and which was associated with behavioral hyperalgesia to thermal and mechanical stimuli. Under this condition, repetitive stimulation of A-fiber primary afferents was capable of producing an enhancement of spinal excitability similar to that evoked by C-fibers in normal animals. Furthermore, we have observed the expression of an NK1 receptor component to the C-fiber evoked response following the establishment of the peripheral injury. The enhanced ventral root responses and changes in receptor sensitivity may contribute to the phenomenon of central sensitization and may be directly related to the behavioral hyperalgesia observed. Moreover, these findings may be relevant to the mechanisms of enhanced central excitability that occur in clinical conditions of inflammatory hyperalgesia and neuropathic pain.

Tachykinin receptor 1

10.1523/jneurosci.14-06-03672.1994

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Citations (144)

Interactions of Central Depressants with Amino Acids and Their Antagonists

Springer eBooks (1978)

A. Dray Norman G. Bowery

10.1007/978-1-4613-4030-0_7

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Citations (3)

Pro-nociceptive effects of neuromedin u in rat

Neuroscience (2003)

Yu Xiang Chang Cao Françoise Mennicken Carole Puma A. Dray

10.1016/s0306-4522(03)00300-2

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Citations (56)

The pro-enkephalin A derivative, peptide E, is centrally processed to active fragments.

PubMed (1984)

Thomas P. Davis F. Porreca A. Dray

Derivative (finance)

Source

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Citations (2)

Actions of enkephalin and morphine on spinal cord and brain stem neurones [proceedings].

PubMed (1976)

J. Davies A. Dray

Source

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Citations (1)

The physiology and pharmacology of mammalian basal ganglia

Progress in Neurobiology (1980)

A. Dray

Sleep

Neuromodulation

10.1016/0301-0082(80)90017-9

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Citations (292)

Differential sensitivity of presumed dopaminergic and non-dopaminergic neurones in rat substantia nigra to electrophoretically applied substance P

Neuroscience Letters (1982)

R.D. Pinnock A. Dray

Pars compacta

Pars reticulata

Tegmentum

Microelectrophoresis

10.1016/0304-3940(82)90345-7

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Citations (52)

Studies of the effects of morphine and related substances on single neurones in the brainstem

Philip Bradley G.J. Bramwell A. Dray

A number of studies have implicated the brainstem in the antinociceptive actions of morphine and possibly with dependence as well (Hertz, Albus, Metys, Schubert and Teschemacher, 1970; Benjamin, 1970). This region of the brain therefore seemed appropriate for an examination of the effects of morphine and related substances, applied microiontophoretically to single neurones. Furthermore, since the actions of morphine have been linked with those of various putative neurotransmitters in the brain, it was decided to study interactions between morphine and three transmitter substances, acetylcholine (ACh) noradrenaline (NA) and 5-hydroxytryptamine (5-HT), all applied iontophoretically to spontaneously active single neurones in urethane-anaesthetised rats. The experimental techniques for microiontophoretic studies of single neurones in urethane-anaesthetised rats have been described in detail elsewhere (Bradley and Dray, 1973). The cells studied were located in the reticular formation and the majority were identified histologically (Boakes, Bramwell, Briggs, Candy and Tempesta, 1974). Morphine-sensitive cells were found grouped around the hypoglossal nerve, in the nucleus reticularis paramedianus and nucleus reticularis gigantocellularis.

10.1007/978-1-349-01247-3_30

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Citations (4)

Bradykinin‐induced activation of nociceptors: receptor and mechanistic studies on the neonatal rat spinal cord‐tail preparation in vitro

British Journal of Pharmacology (1992)

A. Dray I.A. Patel Martin Perkins A. Rueff

1. The effects of bradykinin on nociceptors have been characterized on a preparation of the neonatal rat spinal cord with functionally connected tail maintained in vitro. Administration of bradykinin to the tail activated capsaicin-sensitive peripheral fibres and evoked a concentration-dependent (EC50 = 130 nM) depolarization recorded from a spinal ventral root (L3-L5). 2. The response to bradykinin was unaffected by the peptidase inhibitors, bestatin (0.4 mM), thiorphan (1 microM), phosphoramidon (1 microM) and MERGETPA (10 microM) or by the presence of calcium blocking agents, cadmium (200 microM) and nifedipine (10 microM). 3. Inhibition of cyclo-oxygenase with indomethacin (1-5 microM), aspirin (1-10 microM) and paracetamol (10-50 microM) consistently attenuated responses to bradykinin. 4. The effect of bradykinin was mimicked by the phorbol ester PDBu, an activator of protein kinase C. The response to bradykinin was attenuated following desensitization to PDBu but desensitization to bradykinin did not induce a cross-desensitization to PDBu. The protein kinase C inhibitor staurosporine (10-500 nM) consistently attenuated the effects of PDBu and bradykinin. 5. Bradykinin responses were reversibly enhanced by dibutyryl cyclic AMP (100 microM). However dibutyryl cyclic GMP (0.5 mM) and nitroprusside (10 microM) produced prolonged block of responsiveness to bradykinin. Prolonged superfusion with pertussis toxin did not affect responses to bradykinin. 6. The B1-receptor agonist des Arg9-bradykinin (10-100 microM) was ineffective alone or after prolonged exposure of the tail to lipopolysaccharide (100 ng ml-1) or epidermal growth factor (100 ng ml-1) to induce B1 receptors. The BI-receptor antagonist, des Arg9 Leu8-bradykinin (10 JM) did not attenuate the response to bradykinin. A number of bradykinin B2 antagonists selectively and reversibly attenuated the response to bradykinin. The rank order potency was Hoe 140> LysLys [Hyp3,Thi5 8,D-Phe7]-bradykinin> D-Arg[Hyp3, Thi5'8, D-Phe7]-bradykinin = D-Arg[Hyp2,Thi5'8, D-Phe7]-bradykinin.7. These data show that bradykinin produces concentration-dependent activation of peripheral nociceptors in the neonatal rat tail. The responses were unaffected by calcium channel block and were partially dependent on the production of prostanoids. Bradykinin-evoked responses were consistent with the activation of protein kinase C-dependent mechanisms. Cyclic GMP-dependent mechanisms may be involved in bradykinin-receptor desensitization whereas cyclic-AMP dependent mechanisms increase fibre excitability and facilitate bradykinin-induced responses. The effects of bradykinin were mediated by a B2 receptor.

Phosphoramidon

Bisindolylmaleimide

Neurokinin A

Bradykinin receptor

Staurosporine

Tachyphylaxis

10.1111/j.1476-5381.1992.tb13418.x

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Citations (114)