Comparison of sildenafil, fluoxetine and its co-administration against chronic constriction injury induced neuropathic pain in rats: An influential additive effect

ABSTRACT

Current drug treatment available for neuropathic pain (NP) provides meager and partial pain relief due to incomplete efficacy and dose-dependent adverse effect. Hence, combination therapy can provide prolongation in analgesic effect with milder side effects. The present investigation aimed at observing the effects of sildenafil (SD) on Fluoxetine (FLX) in attenuation of chronic constriction injury (CCI) induced NP in rats. CCI was achieved in rats by placing four loose ligations around the sciatic nerve and rats were received respective treatments on SD and FLX till 14 days further behaviors parameters like heat hyperalgesia and allodynia, pin prick and acetone drop test were executed in order to access thermal, mechanical and cold allodynia, respectively, on a predetermined time interval. On the 21st day the animals were sacrificed for determination of total protein, myeloperoxidase activity in the adjoining muscular tissues while glutathione and TNF-α in the sciatic nerve. Co-administration of SD + FLX + CCI gave the pronounced effect that was superior over individual responses of SD and FLX in all behavioral as well as biochemical parameters. It was observed that attenuation in the altered behavioral pattern of CCI induced rats was modified prominently from 3rd day only in a group of rats treated with SD + FLX + CCI. The whole study was finally supported by histopathological results. Finally, it was concluded that SD produces an additive effect when given with FLX in attenuation of NP may be due to elevation in the level of intracellular concentrations of cyclic guanosine monophosphate which further causes downregulation of calcium channel.

KEYWORDS:

• Sildenafil
• fluoxetine
• sciatic nerve
• chronic constriction injury
• neuropathic pain

Authors’ contributions

Bimlesh Kumar, Amarjeet Singh, Sachin Kumar Singh and Monica Gulati designed the experiments, performed the experiments, analyzed the results, and drafted the manuscript. Indu Melkani and Sakshi Panchal with the help of Sameer Balraj Singh Gill, Jivan Jyoti, Narendra Kumar Pandey, Shubham Kumar and Bhuban Subedi performed the behavioral measure. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Notes on contributors

Indu Melkani

Indu Melkani Presently working as Asst. Prof. in School of Pharmaceutical Sciences, Lovely professional University, Punjab, India. She is Master in Pharmacology (M Pharm) and have several other publications in field of formulation, development and pharmacological investigation.

Bimlesh Kumar

Bimlesh Kumar Dr. Bimlesh Kumar is working as Assoc. Prof. in School of Pharmaceutical Sciences, Lovely professional University, Punjab, India. He has guided 35 M Pharm projects and published more than 45 research papers. He is recipient of Young researcher award of Lovely Professional University from 3 consecutive years. He is also recipient of Young teacher award by Society of Pharmaceutical Education & Research (SPER). He is member of various highly recognized professional national and international societies like IPGA, IPA, SPER and ISCA. His research interests encompass the pharmacological screening of herbal and semisynthetic and synthetic drugs in animal models of various diseases like Gastrointestinal disorders, Diabetes, Neuropathic pain, Colon cancer, epilepsy, Depression and cognitive impairment related disorders.

Sakshi Panchal

Sakshi Panchal She is master in Pharmacology (M Pharm) and completed her degree from School of Pharmaceutical Sciences, Lovely professional University, Punjab, India and have several other publications in field of formulation, development and pharmacological investigation.

Sachin Kumar Singh

Sachin Kumar Singh Dr. Sachin Kumar Singh is working as Associate Professor, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab. He has completed two government funded projects and published more than 75 plus research papers with cumulative impact factor 120 and h index 16 along with 463 citations. Dr. Singh has co-authored seven book chapters and filed four patents. He is also recipient of Young Scientist Award given by Department of Science and Technology, India and Bharat Shiksha Ratan Award. His area of interest includes analytical method development, stability studies and development of novel as well as targeted drug delivery systems for the treatment of diabetes, neuropathic pain and colon cancer. He has guided 30 master’s and 4 PhD. research projects and currently guiding 3 master’s project and 9 PhD. projects.

Amarjeet Singh

Amarjeet Singh He is master in Pharmacology (M Pharm) and completed her degree from School of Pharmaceutical Sciences, Lovely professional University, Punjab, India. Presently working in Parexel International Pvt. Ltd., Chandigarh, India and have several other publications in field of formulation, development and pharmacological investigation.

Monica Gulati

Monica Gulati Dr Monica Gulati is the Registrar and Sr. Dean at the School of Pharmaceutical Sciences, Lovely Professional University, India with more than 20 years of teaching, research and administrative experience. Her research forte is enhancing bio-performance of drug molecules including small and large biomolecules, phytochemicals and probiotics using conventional and novel dosage forms. She holds a keen interest in the quality control parameters of both conventional and novel delivery systems. She is also working in the area of analytical method development of drugs and phytochemicals. Her group has designed novel platform technologies to overcome challenges in therapeutic delivery of different classes of phyto-polypeptides and phytochemicals.

Sameer Balraj Singh Gill

Sameer Balraj Singh Gill He is master in Pharmaceutics (M Pharm) and completed his degree from School of Pharmaceutical Sciences, Lovely professional University, Punjab, India and have several other publications in field of formulation, development and pharmacological investigation.

Jivan Jyoti

Jivan Jyoti Presently working as Asst. Prof. in School of Pharmaceutical Sciences, Lovely professional University, Punjab, India. She is Master in Quality Assurance (M Pharm) and have several other publications in field of formulation, development and pharmacological investigation.

Narendra Kumar Pandey

Narendra Kumar Pandey He is pursuing PhD from School of Pharmaceutical Sciences, Lovely professional University, Punjab, India. Presently working as Assoc. Prof. in School of Pharmaceutical Sciences, Lovely professional University, Punjab, India. He is expert in DoE, pharmaceutical product formulation, characterization and method development on HPLC. His area of interest includes analytical method development, stability studies and development of novel as well as targeted drug delivery systems for the treatment of diabetes, neuropathic pain and colon cancer. He has guided 30 master’s students.

Shubham Kumar

Shubham Kumar He is master in Pharmacology (M Pharm) and completing his degree from School of Pharmaceutical Sciences, Lovely professional University, Punjab, India.

Bhuban Subedi

Bhuban Subedi He is master in Pharmacology (M Pharm) and completing his degree from School of Pharmaceutical Sciences, Lovely professional University, Punjab, India.