Galanin over-expression decreases the development of neuropathic pain-like behaviors in mice after partial sciatic nerve injury

Physiology, Signaling, and Pharmacology of Galanin Peptides and Receptors: Three Decades of Emerging Diversity

“…Mouse lines have been generated that overexpress galanin (either constitutively or inducibly under the control of different promoters; see Table 1), and their electrophysiologic and behavioral phenotypes further support a strong analgesic role for galanin after nerve injury (Blakeman et al, 2001;Grass et al, 2003a;Holmes et al, 2003;Hygge-Blakeman et al, 2004;Pope et al, 2010;Hulse et al, 2011Hulse et al, , 2012 due to peripheral and central actions of the peptide (Hulse et al, 2011). However, contrary to initial predictions, galanin-KO mice display attenuated pain-like behaviors in several nerve-injury models (Kerr et al, 2000a(Kerr et al, , 2001bHolmes et al, 2003;Hulse et al, 2008).…”

“…Furthermore, this increase in regeneration is associated with increased functional recovery as measured by both motor and sensory nerve conduction velocities (Xu et al, 2012b). In contrast, galanin-OE mice did not display an increase in functional recovery after a sciatic nerve crush injury (Hygge- Blakeman et al, 2004). However, these mice ectopically overexpress galanin under the control of the dopamine b-hydroxylase promoter , and it remains to be determined whether galanin levels in the DRG after nerve injury are higher in these mice than in WT mice.…”

“…Several transgenic mouse lines have been generated that overexpress galanin in particular subsets of neurons, and their phenotypes support an inhibitory role for galanin ( Table 1). Mice that constitutively overexpress galanin under the control of the c-Ret (Holmes et al, 2003), PDGF, platelet-derived growth factor subunit-b (Blakeman et al, 2001), or dopamine b-hydroxylase (Hygge- Blakeman et al, 2004) promoters, all display reduced sensitivity to thermal stimulation, and in the case of the c-Ret transgenic mice, also to mechanical stimulation.…”

Changes in galanin immunoreactivity in rat micturition reflex pathways after cyclophosphamide-induced cystitis

“…Pain models for acute and chronic inflammation exhibit an initial decrease in galanin peptide and mRNA in DRG followed by an increase in galanin expression (Ji et al 1995;Calza et al 1998). Transgenic over-expression of galanin in the DRG modulates pain-related behaviors Holmes et al 2003;Hygge-Blakeman et al 2004). Intrathecal injection of galanin results in a biphasic response with facilitation of the nociceptive flexor reflex at low doses and inhibition at high doses (WiesenfeldHallin et al 1989).…”

Galanin – 25 years with a multitalented neuropeptide

“…These data imply that the loss of a subset of sensory neurons that are likely to be nociceptors underlies the absence of allodynia observed in the Gal-KO and GalR2-KO animals. It also explains the apparent discrepancy between the absence of neuropathic pain behaviour in the Gal-KO and GalR2-KO animals and the previous body of published data demonstrating an inhibitory role for galanin in pain processing in the intact animal and in particular after nerve injury [22,26,27]. An analogous survival role in the adult DRG is also evident after nerve injury.…”