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Effects of chronic administration of amitriptyline, gabapentin and minocycline on spinal brain-derived neurotrophic factor expression and neuropathic pain behavior in a rat chronic constriction injury model.
Reg Anesth Pain Med. 2013 Mar-Apr; 38(2):124-30.RA

Abstract

BACKGROUND

In animal models of neuropathic pain (NP), promising results have been reported with the administration of minocycline, possibly through inhibition of spinal brain-derived neurotrophic factor (BDNF) expression. No data are available on the effect of amitriptyline and gabapentin on spinal BDNF expression. If the mechanism of action of the latter drugs does not involve brain-derived NP inhibition, further clinical research in BDNF is warranted.

METHODS

In this placebo-controlled study, we investigated the effects of amitriptyline (5 mg/kg), gabapentin (50 mg/kg), and minocycline (25 mg/kg) twice a day on NP behavior in a sciatic chronic constriction injury (CCI) rat model. Drug treatment started 7 days after CCI and lasted 14 days. At postoperative day 21, spinal BDNF expression in laminae I and II was quantified using immunocytochemistry.

RESULTS

Sciatic CCI resulted in NP behavior throughout the duration of the experiment in the placebo group. When administered for 2 weeks, minocycline (P ≤ 0.001) and amitriptyline (P ≤ 0.05), but not gabapentin, reduced thermal hyperalgesia. None of these drugs reduced mechanical allodynia. As opposed to amitriptyline and gabapentin, 2 weeks of treatment with minocycline reduced brain-derived, neurotrophic factor immunoreactivity (P ≤ 0.05) in the ipsilateral dorsal horn.

CONCLUSIONS

Minocycline and amitriptyline both reduce NP behavior in a sciatic CCI rat model, but only minocycline reduces spinal BDNF, indicating different modes of action of these 2 drugs. The observed actions of minocycline closely fit the clinical needs for the treatment of NP.

Authors+Show Affiliations

Department of Anesthesiology, Intensive Care, Emergency Care and Pain Therapy, Ziekenhuis Oost-Limburg, Genk, Belgium. pascal.vanelderen@gmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23337936

Citation

Vanelderen, Pascal, et al. "Effects of Chronic Administration of Amitriptyline, Gabapentin and Minocycline On Spinal Brain-derived Neurotrophic Factor Expression and Neuropathic Pain Behavior in a Rat Chronic Constriction Injury Model." Regional Anesthesia and Pain Medicine, vol. 38, no. 2, 2013, pp. 124-30.
Vanelderen P, Rouwette T, Kozicz T, et al. Effects of chronic administration of amitriptyline, gabapentin and minocycline on spinal brain-derived neurotrophic factor expression and neuropathic pain behavior in a rat chronic constriction injury model. Reg Anesth Pain Med. 2013;38(2):124-30.
Vanelderen, P., Rouwette, T., Kozicz, T., Heylen, R., Van Zundert, J., Roubos, E. W., & Vissers, K. (2013). Effects of chronic administration of amitriptyline, gabapentin and minocycline on spinal brain-derived neurotrophic factor expression and neuropathic pain behavior in a rat chronic constriction injury model. Regional Anesthesia and Pain Medicine, 38(2), 124-30. https://doi.org/10.1097/AAP.0b013e31827d611b
Vanelderen P, et al. Effects of Chronic Administration of Amitriptyline, Gabapentin and Minocycline On Spinal Brain-derived Neurotrophic Factor Expression and Neuropathic Pain Behavior in a Rat Chronic Constriction Injury Model. Reg Anesth Pain Med. 2013 Mar-Apr;38(2):124-30. PubMed PMID: 23337936.
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TY - JOUR T1 - Effects of chronic administration of amitriptyline, gabapentin and minocycline on spinal brain-derived neurotrophic factor expression and neuropathic pain behavior in a rat chronic constriction injury model. AU - Vanelderen,Pascal, AU - Rouwette,Tom, AU - Kozicz,Tamás, AU - Heylen,René, AU - Van Zundert,Jan, AU - Roubos,Eric W, AU - Vissers,Kris, PY - 2013/1/23/entrez PY - 2013/1/23/pubmed PY - 2013/8/13/medline SP - 124 EP - 30 JF - Regional anesthesia and pain medicine JO - Reg Anesth Pain Med VL - 38 IS - 2 N2 - BACKGROUND: In animal models of neuropathic pain (NP), promising results have been reported with the administration of minocycline, possibly through inhibition of spinal brain-derived neurotrophic factor (BDNF) expression. No data are available on the effect of amitriptyline and gabapentin on spinal BDNF expression. If the mechanism of action of the latter drugs does not involve brain-derived NP inhibition, further clinical research in BDNF is warranted. METHODS: In this placebo-controlled study, we investigated the effects of amitriptyline (5 mg/kg), gabapentin (50 mg/kg), and minocycline (25 mg/kg) twice a day on NP behavior in a sciatic chronic constriction injury (CCI) rat model. Drug treatment started 7 days after CCI and lasted 14 days. At postoperative day 21, spinal BDNF expression in laminae I and II was quantified using immunocytochemistry. RESULTS: Sciatic CCI resulted in NP behavior throughout the duration of the experiment in the placebo group. When administered for 2 weeks, minocycline (P ≤ 0.001) and amitriptyline (P ≤ 0.05), but not gabapentin, reduced thermal hyperalgesia. None of these drugs reduced mechanical allodynia. As opposed to amitriptyline and gabapentin, 2 weeks of treatment with minocycline reduced brain-derived, neurotrophic factor immunoreactivity (P ≤ 0.05) in the ipsilateral dorsal horn. CONCLUSIONS: Minocycline and amitriptyline both reduce NP behavior in a sciatic CCI rat model, but only minocycline reduces spinal BDNF, indicating different modes of action of these 2 drugs. The observed actions of minocycline closely fit the clinical needs for the treatment of NP. SN - 1532-8651 UR - https://www.unboundmedicine.com/medline/citation/23337936/Effects_of_chronic_administration_of_amitriptyline_gabapentin_and_minocycline_on_spinal_brain_derived_neurotrophic_factor_expression_and_neuropathic_pain_behavior_in_a_rat_chronic_constriction_injury_model_ L2 - https://rapm.bmj.com/lookup/pmidlookup?view=long&pmid=23337936 DB - PRIME DP - Unbound Medicine ER -