Tags

Type your tag names separated by a space and hit enter

Gabapentin-induced pharmacodynamic effects in the spinal nerve ligation model of neuropathic pain.
Eur J Pain. 2014 Feb; 18(2):223-37.EJ

Abstract

BACKGROUND

The function of brain networks can be changed in a maladaptive manner in response to chronic neuropathic pain. Analgesics can reduce pain by acting on such networks via direct or indirect (peripheral or spinal) mechanisms. This investigation aimed to map gabapentin's pharmacodynamics (PD) in the rodent brain following induction of neuropathic pain in order to further understand its PD profile.

METHODS

Pharmacological magnetic resonance imaging (phMRI) and a novel functional connectivity analysis procedure were performed following vehicle or gabapentin treatment in the rat spinal nerve ligation (SNL) model of neuropathic pain as well as sham animals.

RESULTS

phMRI performed in SNL animals revealed robust gabapentin-induced responses throughout the hippocampal formation, yet significant (p < 0.05, corrected for multiple comparisons) responses were also measured in other limbic structures and the sensorimotor system. In comparison, sham animals displayed weaker and less widespread phMRI signal changes subsequent to gabapentin treatment. Next, communities of networks possessing strong functional connectivity were elucidated in vehicle-treated SNL and sham animals. We observed that SNL and sham animals possessed distinct functional connectivity signatures. When measuring how gabapentin altered the behaviour of the discovered networks, a decrease in functional connectivity driven by gabapentin was not only observed, but the magnitude of this PD effect was greater in SNL animals.

CONCLUSIONS

Using phMRI and functional connectivity analysis approaches, the PD effects of gabapentin in a preclinical neuropathic pain state were characterized. Furthermore, the current results offer insights on which brain systems gabapentin directly or indirectly acts upon.

Authors+Show Affiliations

Integrated Science and Technology, Abbvie Inc., North Chicago, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23857727

Citation

Hooker, B A., et al. "Gabapentin-induced Pharmacodynamic Effects in the Spinal Nerve Ligation Model of Neuropathic Pain." European Journal of Pain (London, England), vol. 18, no. 2, 2014, pp. 223-37.
Hooker BA, Tobon G, Baker SJ, et al. Gabapentin-induced pharmacodynamic effects in the spinal nerve ligation model of neuropathic pain. Eur J Pain. 2014;18(2):223-37.
Hooker, B. A., Tobon, G., Baker, S. J., Zhu, C., Hesterman, J., Schmidt, K., Rajagovindan, R., Chandran, P., Joshi, S. K., Bannon, A. W., Hoppin, J., Beaver, J., Fox, G. B., Day, M., & Upadhyay, J. (2014). Gabapentin-induced pharmacodynamic effects in the spinal nerve ligation model of neuropathic pain. European Journal of Pain (London, England), 18(2), 223-37. https://doi.org/10.1002/j.1532-2149.2013.00364.x
Hooker BA, et al. Gabapentin-induced Pharmacodynamic Effects in the Spinal Nerve Ligation Model of Neuropathic Pain. Eur J Pain. 2014;18(2):223-37. PubMed PMID: 23857727.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gabapentin-induced pharmacodynamic effects in the spinal nerve ligation model of neuropathic pain. AU - Hooker,B A, AU - Tobon,G, AU - Baker,S J, AU - Zhu,C, AU - Hesterman,J, AU - Schmidt,K, AU - Rajagovindan,R, AU - Chandran,P, AU - Joshi,S K, AU - Bannon,A W, AU - Hoppin,J, AU - Beaver,J, AU - Fox,G B, AU - Day,M, AU - Upadhyay,J, Y1 - 2013/07/16/ PY - 2013/06/19/accepted PY - 2013/7/17/entrez PY - 2013/7/17/pubmed PY - 2014/9/5/medline SP - 223 EP - 37 JF - European journal of pain (London, England) JO - Eur J Pain VL - 18 IS - 2 N2 - BACKGROUND: The function of brain networks can be changed in a maladaptive manner in response to chronic neuropathic pain. Analgesics can reduce pain by acting on such networks via direct or indirect (peripheral or spinal) mechanisms. This investigation aimed to map gabapentin's pharmacodynamics (PD) in the rodent brain following induction of neuropathic pain in order to further understand its PD profile. METHODS: Pharmacological magnetic resonance imaging (phMRI) and a novel functional connectivity analysis procedure were performed following vehicle or gabapentin treatment in the rat spinal nerve ligation (SNL) model of neuropathic pain as well as sham animals. RESULTS: phMRI performed in SNL animals revealed robust gabapentin-induced responses throughout the hippocampal formation, yet significant (p < 0.05, corrected for multiple comparisons) responses were also measured in other limbic structures and the sensorimotor system. In comparison, sham animals displayed weaker and less widespread phMRI signal changes subsequent to gabapentin treatment. Next, communities of networks possessing strong functional connectivity were elucidated in vehicle-treated SNL and sham animals. We observed that SNL and sham animals possessed distinct functional connectivity signatures. When measuring how gabapentin altered the behaviour of the discovered networks, a decrease in functional connectivity driven by gabapentin was not only observed, but the magnitude of this PD effect was greater in SNL animals. CONCLUSIONS: Using phMRI and functional connectivity analysis approaches, the PD effects of gabapentin in a preclinical neuropathic pain state were characterized. Furthermore, the current results offer insights on which brain systems gabapentin directly or indirectly acts upon. SN - 1532-2149 UR - https://www.unboundmedicine.com/medline/citation/23857727/Gabapentin_induced_pharmacodynamic_effects_in_the_spinal_nerve_ligation_model_of_neuropathic_pain_ L2 - https://doi.org/10.1002/j.1532-2149.2013.00364.x DB - PRIME DP - Unbound Medicine ER -