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The effects of dexmedetomidine alone and in combination with tramadol or amitriptyline in a neuropathic pain model.
Pain Physician. 2014 Mar-Apr; 17(2):187-95.PP

Abstract

BACKGROUND

Interactions between the sympathetic and somatic nervous system play an essential role in the pathophysiologic mechanisms of neuropathic pain. The α2-adrenoceptor agonists produce effective antinociception, but sedation is an important adverse effect. Multidrug therapy is potentially valuable to decrease side effects.

OBJECTIVE

The aim of the present study was to investigate the possible antinociceptive effect of dexmedetomidine, an α2-adrenoceptor agonist, and its combination with front-line treatment of neuropathic pain, i.e., amitriptyline or tramadol, in a chronic constriction injury (CCI) model of the sciatic nerve in rats.

STUDY DESIGN

Controlled animal study.

METHODS

Following unilateral ligation of the left sciatic nerve, the effect of intraperitoneal (i.p.) dexmedetomidine (5 ug/kg), tramadol (5 mg/kg), and amitriptyline (30 mg/kg) on mechanical allodynia (measured by electrical von Frey apparatus) and hyperalgesia (measured by Randall and Selitto test) was studied.

RESULTS

The sham-operated rats and un-operated hind paw (right paw) press normally on the floor reproduced by a weighted pain score of 0. Behavioral and mechanical tests confirmed the development of neuropathic pain after CCI. All individual drugs and dexmedetomidine combination with either tramadol or amitriptyline were effective in reducing mechanical allodynia and hyperalgesia. Dexmedetomidine, amitriptyline, tramadol, amitriptyline+dexmedetomidine, and tramadol+dexmedetomidine combination did not produce any sedation/motor impairment (P > 0.05).

LIMITATIONS

Although the combination of these drugs improved the CCI model of neuropathic pain in this study, an additional interpretation of the underlying mechanism(s) will be needed to confirm these findings.

CONCLUSION

The combination of these drugs appears to be more effective in increasing the pain threshold after peripheral nerve injury, when compared with the administration of either of amitriptyline or tramadol alone and should be considered as a possible alternative to decrease side effects of individual drug therapy.

Authors+Show Affiliations

Pharmacology Department, Faculty of Medicine, Assiut University, Egypt.No 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

24658480

Citation

Farghaly, Hanan Sm, et al. "The Effects of Dexmedetomidine Alone and in Combination With Tramadol or Amitriptyline in a Neuropathic Pain Model." Pain Physician, vol. 17, no. 2, 2014, pp. 187-95.
Farghaly HS, Abd-Ellatief RB, Moftah MZ, et al. The effects of dexmedetomidine alone and in combination with tramadol or amitriptyline in a neuropathic pain model. Pain Physician. 2014;17(2):187-95.
Farghaly, H. S., Abd-Ellatief, R. B., Moftah, M. Z., Mostafa, M. G., Khedr, E. M., & Kotb, H. I. (2014). The effects of dexmedetomidine alone and in combination with tramadol or amitriptyline in a neuropathic pain model. Pain Physician, 17(2), 187-95.
Farghaly HS, et al. The Effects of Dexmedetomidine Alone and in Combination With Tramadol or Amitriptyline in a Neuropathic Pain Model. Pain Physician. 2014 Mar-Apr;17(2):187-95. PubMed PMID: 24658480.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effects of dexmedetomidine alone and in combination with tramadol or amitriptyline in a neuropathic pain model. AU - Farghaly,Hanan Sm, AU - Abd-Ellatief,Rasha B, AU - Moftah,Marie Z, AU - Mostafa,Mostafa G, AU - Khedr,Eman M, AU - Kotb,Hassan I, PY - 2014/3/25/entrez PY - 2014/3/25/pubmed PY - 2014/11/18/medline SP - 187 EP - 95 JF - Pain physician JO - Pain Physician VL - 17 IS - 2 N2 - BACKGROUND: Interactions between the sympathetic and somatic nervous system play an essential role in the pathophysiologic mechanisms of neuropathic pain. The α2-adrenoceptor agonists produce effective antinociception, but sedation is an important adverse effect. Multidrug therapy is potentially valuable to decrease side effects. OBJECTIVE: The aim of the present study was to investigate the possible antinociceptive effect of dexmedetomidine, an α2-adrenoceptor agonist, and its combination with front-line treatment of neuropathic pain, i.e., amitriptyline or tramadol, in a chronic constriction injury (CCI) model of the sciatic nerve in rats. STUDY DESIGN: Controlled animal study. METHODS: Following unilateral ligation of the left sciatic nerve, the effect of intraperitoneal (i.p.) dexmedetomidine (5 ug/kg), tramadol (5 mg/kg), and amitriptyline (30 mg/kg) on mechanical allodynia (measured by electrical von Frey apparatus) and hyperalgesia (measured by Randall and Selitto test) was studied. RESULTS: The sham-operated rats and un-operated hind paw (right paw) press normally on the floor reproduced by a weighted pain score of 0. Behavioral and mechanical tests confirmed the development of neuropathic pain after CCI. All individual drugs and dexmedetomidine combination with either tramadol or amitriptyline were effective in reducing mechanical allodynia and hyperalgesia. Dexmedetomidine, amitriptyline, tramadol, amitriptyline+dexmedetomidine, and tramadol+dexmedetomidine combination did not produce any sedation/motor impairment (P > 0.05). LIMITATIONS: Although the combination of these drugs improved the CCI model of neuropathic pain in this study, an additional interpretation of the underlying mechanism(s) will be needed to confirm these findings. CONCLUSION: The combination of these drugs appears to be more effective in increasing the pain threshold after peripheral nerve injury, when compared with the administration of either of amitriptyline or tramadol alone and should be considered as a possible alternative to decrease side effects of individual drug therapy. SN - 2150-1149 UR - https://www.unboundmedicine.com/medline/citation/24658480/The_effects_of_dexmedetomidine_alone_and_in_combination_with_tramadol_or_amitriptyline_in_a_neuropathic_pain_model_ L2 - http://www.painphysicianjournal.com/linkout?issn=1533-3159&vol=17&page=187 DB - PRIME DP - Unbound Medicine ER -