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Pharmacodynamic effect of gabapentin on central nervous system in patients with chronic low back pain: a [99mTc]Tc-ECD SPECT study
  1. Priscila Papassidero1,
  2. Lauro Wichert-Ana2,
  3. Erica Negrini Lia3,
  4. Leonardo Alexandre-Santos2,
  5. Ana Carolina Trevisan2,
  6. Eduardo Barbosa Coelho4,
  7. Oscar Della Pasqua5,6,
  8. Vera Lúcia Lanchote7 and
  9. Fabíola Dach1
  1. 1 Department of Neurosciences and Behavioral Sciences, USP Ribeirao Preto, Ribeirao Preto, Brazil
  2. 2 Nuclear Medicine and PET/CT Laboratory, Department of Medical Imaging, Hematology and Clinical Oncology, USP Ribeirao Preto, Ribeirao Preto, Brazil
  3. 3 Department of Dentistry, School of Health Sciences, University of Brasilia, Brasilia, Brazil
  4. 4 Department of Internal Medicine, USP Ribeirao Preto, Ribeirao Preto, Brazil
  5. 5 Department of Pharmacology, UCL School of Pharmacy, London, UK
  6. 6 Clinical Pharmacology Modelling & Simulation, GlaxoSmithKline Plc, London, UK
  7. 7 Department of Clinical Analysis, Food Science and Toxicology, USP Ribeirao Preto, Ribeirao Preto, Brazil
  1. Correspondence to Dr Priscila Papassidero, Department of Neurosciences and Behavioral Sciences, USP Ribeirao Preto, Ribeirao Preto, 14048-900, Brazil; priscila.pcp{at}hotmail.com

Abstract

Background Gabapentin is an effective therapeutic alternative for chronic low back pain, indicated in several guidelines for treating neuropathic pain as first-line medication. This study aimed to describe the pharmacodynamics of gabapentin in the central nervous system of patients with chronic low back pain (CLBP) by using single-photon emission CT (SPECT) with [99mTc]Tc-ECD.

Methods We selected 13 patients with CLBP due to lumbar disc herniation. They underwent SPECT before and after using gabapentin, compared with a SPECT database of healthy volunteers. A second analysis compared regional cerebral blood flow (rCBF) changes between responders and non-responders to gabapentin and the healthy controls.

Results The mean age of patients was 41 years, and the mean pain intensity was 5.92 points, measured by the Numeric Rating Scale. After using gabapentin, SPECT showed an increase of rCBF in the bilateral anterior cingulate gyrus and a decrease of rCBF in periaqueductal gray matter. Non-responder patients with gabapentin showed a post-treatment decrease of rCBF in the paracentral lobule of the brain.

Conclusions A lack of improvement in some patients with gabapentin may be associated with an activated affective circuit of pain, evidenced by the increase of rCBF of the anterior cingulate cortex. A maladaptive brain state in chronic pain can explain the decrease of rCBF in the default mode network structures. Gabapentin acts directly or indirectly on neurons of periaqueductal gray substance by increasing the pain threshold and decreasing the rCBF of this structure.

  • Back Pain
  • CHRONIC PAIN
  • Pharmacology

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

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Footnotes

  • Contributors PP is the guarantor of this article. PP, FD, LW-A and ODP contributed to the study conception and design. ACT and LA-S contributed to the data processing. PP, FD, ENL, EBC, VLL and LW-A contributed to the data presentation and writing of the manuscript. PP and LW-A contributed to the figures. All authors read and approved the final manuscript.

  • Funding The authors gratefully acknowledge financial support from: (A) Grant #049/2013 (AUXPE No. 2880/2013) from CAPES / NUFFIC, Brazil Netherlands International Cooperation; (B) Grant #2015/50089-3 and Grant #2021/12671-3, São Paulo Research Foundation (FAPESP).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.