Increased Expression of the Neuroregenerative Peptide Galanin in the Major Pelvic Ganglion Following Cavernous Nerve Injury Emmanuel Weyne, MD,* 1 Maarten Albersen, MD, PhD,* 1 Johanna L. Hannan, PhD, † Fabio Castiglione, MD, ‡ Petter Hedlund, MD, PhD, ‡ Godelieve Verbist, BSc, § Dirk De Ridder, MD, PhD,* Trinity J. Bivalacqua, MD, PhD, † and Frank Van der Aa, MD, PhD* *Laboratory for Experimental Urology, Department of Development and Regeneration, University of Leuven, Leuven, Belgium; † The James Buchanan Brady Urological Institute, Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD, USA; ‡ Urological Research Institute, San Raffaele Scientific Institution, Milan, Italy; § Laboratory for Experimental Gynecology, Department of Development and Regeneration, University of Leuven, Leuven, Belgium DOI: 10.1111/jsm.12570 ABSTRACT Introduction. Erectile dysfunction (ED) remains a frequent complication of radical prostatectomy due to injury to the cavernous nerves (CNs). A recent microarray showed the neuropeptide galanin to be one of the most strikingly upregulated genes in the rat major pelvic ganglion (MPG) after bilateral CN crush injury (BCNI). Aim. The aim of this study is to evaluate the temporal regulation of galanin in the MPG after BCNI and its relationship to functional nerve regeneration. Methods. Changes in galanin, galanin receptor (galR), and c-JUN mRNA expression were assessed in Sprague- Dawley rats after sham operation (n = 10) and at 48 hours (n = 10), 7 (n = 10), 14 (n = 5), 21 (n = 5), 30 (n = 5), and 60 (n = 5) days after BCNI using quantitative PCR. Erectile function was assessed by measuring intracavernous pressure (ICP) divided by mean arterial pressure (MAP) during CN electrostimulation. Immunohistochemistry was performed on the MPG in sham-operated animals and 5 days after BCNI. Main Outcome Measures. ICP/MAP upon CN stimulation; galanin, galR1, -2, -3, and c-JUN mRNA expression at various time points after BCNI; and nNOS, galanin, and galR distribution in the MPG of sham-operated rats and after BCNI. Results. After BCNI, ICP/MAP values quickly deteriorate, while after 60 days, spontaneous restoration of erectile responses to CN stimulation is observed, reflecting CN regeneration. Galanin mRNA in the MPG is up to 186-fold upregulated compared with sham-operated rats at 48 hours and 7 days after BCNI and gradually declines with increasing time from injury, whereas galanin receptor expressions decrease and c-JUN gradually increases. Galanin expression shows a strong inverse correlation with erectile responses to CN stimulation with time from injury. Injured MPGs show a colocalization between galanin- and nNOS-positive neuronal cell population in the MPG. Conclusions. Galanin is upregulated in the MPG in the early phase after CN injury after which it gradually decreases and is present in nNOS-positive neurons of the ganglion. We hypothesize that galanin upregulation is an important factor in the endogenous neuroregenerative response to CN injury. Weyne E, Albersen M, Hannan JL, Castiglione F, Hedlund P, Verbist G, De Ridder D, Bivalacqua TJ, and Van der Aa F. Increased expression of the neuroregenerative peptide galanin in the major pelvic ganglion following cavernous nerve injury. J Sex Med 2014;11:1685–1693. Key Words. Autonomic Nerve Regeneration; c-JUN; Galanin Receptor; Major Pelvic Ganglion; Neurogenic Erectile Dysfunction; Neuroregeneration; Neuronal Nitric Oxide Synthase; Parasympathetic; Radical Prostatec- tomy; Cavernous Nerve Injury 1 Equal contributions. 1685 © 2014 International Society for Sexual Medicine J Sex Med 2014;11:1685–1693