Introduction like immunoreactivity LI [3,29], galanin mRNA [36] and
Brain Research 886 2000 67–72 www.elsevier.com locate bres
Interactive report
Effect of intrathecal galanin and its putative antagonist M35 on pain
1
behavior in a neuropathic pain model
¨ Hong-Xiang Liu, Tomas Hokfelt
Department of Neuroscience , Karolinska Institutet, S-171 77 Stockholm, Sweden
Accepted 8 August 2000
Abstract
There is currently some debate over a possible role of galanin in pain processing. It was recently reported that the levels of galanin in dorsal root ganglia DRGs seem related to development of allodynia after unilateral sciatic nerve constriction injury. In our present study,
we aimed at characterizing the effect of exogenous and endogenous galanin on pain behavior in allodynic and non-allodynic rats in which the levels of galanin in DRG neurons are low and high, respectively [28]. The results show that in allodynic rats, the mechanical threshold
increases dose-dependently after intrathecal i.t. injection of galanin, while no significant changes were observed in groups treated with the putative galanin antagonist M35 or saline. In non-allodynic rats i.t. injection of M35 induced a significant mechanical allodynic state,
which did not occur after injection of galanin, bradykinin, the bradykinin fragment2–9 or saline. The results suggest that in the present experimental paradigm exogenous galanin has an anti-allodynic effect in the allodynic rats, and that endogenous galanin has a tonic
inhibitory effect in the non-allodynic group.
2000 Elsevier Science B.V. All rights reserved.
Theme : Sensory systems
Topic : Pain modulation: pharmacology
Keywords : Allodynia; Dorsal root ganglion; Nerve injury; Neuropeptide; Spinal cord
1. Introduction like immunoreactivity LI [3,29], galanin mRNA [36] and
galanin receptor mRNAs are expressed in dorsal root Neuropeptides are widely distributed in the nervous
ganglion DRG neurons, and also in dorsal horn inter- system, virtually always coexisting with one or more
neurons express
galanin [3,7,21,23,25,27,30,37,45,49].
classic transmitters see [11]. Their exact functional role Galanin expression is strongly upregulated in DRG neu-
has often not been defined, but they may both act as rons [10,36], and its basal release is increased in the dorsal
trophic molecules see [26,32] and or as slow, mostly horn after peripheral nerve injury [4]. Many studies have
extrasynaptically released see [34] messengers see focussed on a possible functional role of galanin in sensory
[17,19], especially in situations when neurons are exposed processing in the dorsal horn of the spinal cord showing
to, in the broadest sense, ‘stressful’ stimuli see [11]. In that the effects of galanin on nociception are complex, and
the present study we focus on one such situation, neuro- both facilitory, inhibitory and bi-phasic responses have
pathic pain, and the possible involvement of the 29- been reported see [41,44].
aminoacid peptide galanin [33] as a putative endogenous Several models of partial nerve injury have been de-
pain antagonist see [41,44]. veloped, which can be used for the assessment of the
Immunohistochemical studies have shown that galanin- effects of analgesics on abnormal pain-like behaviors
allodynia and hyperalgesia. One example is loose chronic constriction nerve injury CCI [2]. In this so-called
1
Published on the World Wide Web on 13 September 2000.
Bennett model allodynia is induced only in some rats,
Abbreviations: ANOVA, analysis of variance; CCI, chronic constriction
which allows comparison between the two groups treated
injury; DRG, dorsal root ganglion; i.t., intrathecal; i.p., intraperitoneal
in an apparently identical way, that is allodynic versus
Corresponding author. Tel.: 146-8-728-7070; fax: 146-8-331-692. ¨
E-mail address : tomas.hokfeltneuro.ki.se T. Hokfelt.
non-allodynic rats. Recently Shi et al. [28] found that
0006-8993 00 – see front matter
2000 Elsevier Science B.V. All rights reserved. P I I : S 0 0 0 6 - 8 9 9 3 0 0 0 2 7 9 1 - 8
68 H
following sciatic nerve CCI galanin expression in DRG manner from below at the center of the plantar surface of
neurons is more strongly upregulated in non-allodynic rats hindpaw ipsi-lateral to the nerve injury. Each filament was
when compared to the allodynic group. In the present study delivered three times with approximately 2-s intervals. The
we used the same model to examine the effect of i.t. lowest force at which each of the three applications of the
galanin and a putative galanin antagonist, M35 [1], in both filament elicited a paw withdrawal was taken as the
allodynic and non-allodynic rats. mechanical response threshold.
2.4. Experimental design