Galanin-mediated Control of Pain: Enhanced Role After Nerve Injury

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1992 Apr 15

PMID 1373497

Citations 32

Authors

Z Wiesenfeld-Hallin

X J Xu

U Langel

K Bedecs

T Hokfelt

T Bartfai

Affiliations

Soon will be listed here.

Abstract

The endogenous inhibitory role of the neuropeptide galanin in pain transmission and spinal cord excitability was demonstrated by the use of a high-affinity galanin receptor antagonist, M-35 [galanin-(1-13)-bradykinin-(2-9)-amide]. M-35, which displaced 125I-labeled galanin from membranes of rat dorsal spinal cord with an IC50 of 0.3 nM, dose-dependently antagonized the effect of intrathecal galanin on the flexor reflex. M-35 potentiated the facilitation of the flexor reflex by conditioning stimulation of cutaneous unmyelinated afferents in rats with intact nerves and the potentiating effect of M-35 on the conditioning-stimulation-induced reflex facilitation of the cutaneous unmyelinated afferents was strongly enhanced after axotomy. These results demonstrate that endogenous galanin plays a tonic inhibitory role in the mediation of spinal cord excitability, and it is particularly noteworthy that this function of galanin is remarkably enhanced after peripheral nerve section.

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References

Giuliani S, Amann R, Papini A, Maggi C, Meli A . Modulatory action of galanin on responses due to antidromic activation of peripheral terminals of capsaicin-sensitive sensory nerves. Eur J Pharmacol. 1989; 163(1):91-6. DOI: 10.1016/0014-2999(89)90399-3. View

Chng J, Christofides N, Anand P, Gibson S, Allen Y, Su H . Distribution of galanin immunoreactivity in the central nervous system and the responses of galanin-containing neuronal pathways to injury. Neuroscience. 1985; 16(2):343-54. DOI: 10.1016/0306-4522(85)90007-7. View

Konopka L, McKeon T, Parsons R . Galanin-induced hyperpolarization and decreased membrane excitability of neurones in mudpuppy cardiac ganglia. J Physiol. 1989; 410:107-22. PMC: 1190469. DOI: 10.1113/jphysiol.1989.sp017523. View

Wiesenfeld-Hallin Z, Villar M, Hokfelt T . The effects of intrathecal galanin and C-fiber stimulation on the flexor reflex in the rat. Brain Res. 1989; 486(2):205-13. DOI: 10.1016/0006-8993(89)90506-4. View

Ahren B, Arkhammar P, Berggren P, Nilsson T . Galanin inhibits glucose-stimulated insulin release by a mechanism involving hyperpolarization and lowering of cytoplasmic free Ca2+ concentration. Biochem Biophys Res Commun. 1986; 140(3):1059-63. DOI: 10.1016/0006-291x(86)90742-4. View

Shehab S, Atkinson M . Vasoactive intestinal polypeptide (VIP) increases in the spinal cord after peripheral axotomy of the sciatic nerve originate from primary afferent neurons. Brain Res. 1986; 372(1):37-44. DOI: 10.1016/0006-8993(86)91456-3. View

Xu X, Hao J, Wiesenfeld-Hallin Z, Hakanson R, Folkers K, Hokfelt T . Spantide II, a novel tachykinin antagonist, and galanin inhibit plasma extravasation induced by antidromic C-fiber stimulation in rat hindpaw. Neuroscience. 1991; 42(3):731-7. DOI: 10.1016/0306-4522(91)90041-l. View

Wiesenfeld-Hallin Z, Villar M, Fahrenkrug J, Hokfelt T . On the Role of Galanin, Substance P and Other Neuropeptides in Primary Sensory Neurons of the Rat: Studies on Spinal Reflex Excitability and Peripheral Axotomy. Eur J Neurosci. 1990; 2(9):733-743. DOI: 10.1111/j.1460-9568.1990.tb00464.x. View

Kuraishi Y, Kawamura M, Yamaguchi T, Houtani T, Kawabata S, Futaki S . Intrathecal injections of galanin and its antiserum affect nociceptive response of rat to mechanical, but not thermal, stimuli. Pain. 1991; 44(3):321-324. DOI: 10.1016/0304-3959(91)90103-5. View

10.

Villar M, Wiesenfeld-Hallin Z, Xu X, Theodorsson E, Emson P, Hokfelt T . Further studies on galanin-, substance P-, and CGRP-like immunoreactivities in primary sensory neurons and spinal cord: effects of dorsal rhizotomies and sciatic nerve lesions. Exp Neurol. 1991; 112(1):29-39. DOI: 10.1016/0014-4886(91)90111-o. View

11.

Steranka L, Manning D, Dehaas C, Ferkany J, Borosky S, Connor J . Bradykinin as a pain mediator: receptors are localized to sensory neurons, and antagonists have analgesic actions. Proc Natl Acad Sci U S A. 1988; 85(9):3245-9. PMC: 280181. DOI: 10.1073/pnas.85.9.3245. View

12.

Yanagisawa M, Yagi N, Otsuka M, Yanaihara C, Yanaihara N . Inhibitory effects of galanin on the isolated spinal cord of the newborn rat. Neurosci Lett. 1986; 70(2):278-82. DOI: 10.1016/0304-3940(86)90477-5. View

13.

Xu X, Wiesenfeld-Hallin Z, Hokfelt T . Intrathecal galanin blocks the prolonged increase in spinal cord flexor reflex excitability induced by conditioning stimulation of unmyelinated muscle afferents in the rat. Brain Res. 1991; 541(2):350-3. DOI: 10.1016/0006-8993(91)91037-2. View

14.

Dunne M, Bullett M, Li G, Wollheim C, Petersen O . Galanin activates nucleotide-dependent K+ channels in insulin-secreting cells via a pertussis toxin-sensitive G-protein. EMBO J. 1989; 8(2):413-20. PMC: 400821. DOI: 10.1002/j.1460-2075.1989.tb03392.x. View

15.

SHARP G, Le Marchand-Brustel Y, Yada T, Russo L, Bliss C, Cormont M . Galanin can inhibit insulin release by a mechanism other than membrane hyperpolarization or inhibition of adenylate cyclase. J Biol Chem. 1989; 264(13):7302-9. View

16.

Hokfelt T, Wiesenfeld-Hallin Z, Villar M, Melander T . Increase of galanin-like immunoreactivity in rat dorsal root ganglion cells after peripheral axotomy. Neurosci Lett. 1987; 83(3):217-20. DOI: 10.1016/0304-3940(87)90088-7. View

17.

Melander T, Hokfelt T, Rokaeus A . Distribution of galaninlike immunoreactivity in the rat central nervous system. J Comp Neurol. 1986; 248(4):475-517. DOI: 10.1002/cne.902480404. View

18.

Skofitsch G, Jacobowitz D . Galanin-like immunoreactivity in capsaicin sensitive sensory neurons and ganglia. Brain Res Bull. 1985; 15(2):191-5. DOI: 10.1016/0361-9230(85)90135-2. View

19.

Post C, Alari L, Hokfelt T . Intrathecal galanin increases the latency in the tail-flick and hot-plate test in mouse. Acta Physiol Scand. 1988; 132(4):583-4. DOI: 10.1111/j.1748-1716.1988.tb08369.x. View

20.

Wiesenfeld-Hallin Z, Xu X, Villar M, Hokfelt T . The effect of intrathecal galanin on the flexor reflex in rat: increased depression after sciatic nerve section. Neurosci Lett. 1989; 105(1-2):149-54. DOI: 10.1016/0304-3940(89)90027-x. View