Operant self-administration of a sigma ligand improves nociceptive and emotional manifestations of neuropathic pain
Article first published online: 22 NOV 2012
© 2012 European Federation of International Association for the Study of Pain Chapters
European Journal of Pain
Volume 17, Issue 6, pages 832–843, July 2013
How to Cite
Bura, A.S., Guegan, T., Zamanillo, D., Vela, J.M. and Maldonado, R. (2013), Operant self-administration of a sigma ligand improves nociceptive and emotional manifestations of neuropathic pain. European Journal of Pain, 17: 832–843. doi: 10.1002/j.1532-2149.2012.00251.x
S1RA was provided by Esteve as a gift within research projects funded by the CENIT program (CEN-20061005) from the Centro para el Desarollo Technológico Industrial from the Spanish Ministry of Science and Innovation (#SAF2007-64062), ‘Redes temáticas de investigación cooperativa en salud (RETICS) del Instituto de Salud Carlos III (RD06/001/001). Red de trastornos adictivos (RTA)’, the Catalan Government (SGR2009-00131), the ICREA Foundation (ICREA Academia-2008) and the DG Research of the European Commission (PHECOMP, #LSHM-CT-2007-037669).
Conflicts of interest
D.Z. and J.M.V. are employees of the company ‘Esteve’.
- Issue published online: 9 MAY 2013
- Article first published online: 22 NOV 2012
- Manuscript Accepted: 28 OCT 2012
- Spanish Ministry of Science and Innovation. Grant Number: SAF2007-64062
- Instituto de Salud Carlos III. Grant Number: RD06/001/001
- Catalan Government. Grant Number: SGR2009-00131
- ICREA Foundation. Grant Number: ICREA Academia-2008
- DG Research of the European Commission (PHECOMP). Grant Number: LSHM-CT-2007-037669
The treatment of neuropathic pain is unsatisfactory at the present moment and the sigma 1 receptor has been identified as a new potential target for neuropathic pain. The aim of this study was to use an operant self-administration model to reveal the potential interest of a new sigma 1 receptor antagonist, S1RA, in chronic pain that was developed in mice by a partial ligation of the sciatic nerve.
Once that chronic pain had reached a steady state, mice were trained to maintain an operant behaviour to self-administer S1RA. The possible abuse liability of the analgesic compound was determined by evaluating operant self-administration in sham-operated mice. The influence of S1RA on the anhedonic state related to chronic pain was also evaluated by measuring the preference for palatable drink (2% sucrose solution) using a recently validated and highly sensitive behavioural device.
Nerve-injured mice, but not sham-operated animals, acquired the operant responding to obtain S1RA (6 mg/kg/infusion). After 10 days of S1RA self-administration, neuropathic pain was significantly reduced in nerve-injured mice. In addition, an anhedonic state was revealed in nerve-injured mice by a decreased consumption of palatable drink, which was significantly attenuated by S1RA (25 mg/kg).
These results reveal the analgesic efficacy of the sigma antagonist, S1RA, in neuropathic pain associated with an improvement of the emotional negative state and that was devoided of reinforcing effects. The operant responses evaluated in this new mouse model can have a high predictive value to estimate the clinical benefit/risk ratio of new analgesic compounds to treat chronic pain, such as S1RA.