Active substance: Gabapentin
Abstract Background Chemotherapy induced peripheral neuropathy CIPN has been attributed to chemotherapeutic agents such as cisplatin which adversely affect disease outcome leading to increased cancer related morbidity.
Preclinical studies have demonstrated that gabapentin is able to attenuate both the positive and negative neuropathic symptoms of CIPN.
However, there is conflicting evidence of gabapentin efficacy in clinical trials, with some studies showing a meaningful reduction in pain scores in patients, while others have obtained negative results. Irrespective of these observations, gabapentin has been considered a common choice of clinicians to manage the positive symptoms associated with CIPN.
However, the therapeutic efficacy of anti-neuropathic doses of gabapentin is greatly hindered by side-effects such as dizziness, somnolence, ataxia, weight gain, lethargy, and convulsions.
There is a recent trend for targeting the peripheral nervous system in neuropathic pain and from this perspective, various topical agents have been compounded and successfully tested in patients and various animal models.
Nociceptors in layers of the skin contain various types of receptor that bind different ligands which influence the generation of pain transmitting action potentials.
Topical formulations traverse epidermal tissue and increase the nociceptive threshold by stabilizing the membranes of specific nociceptors.
The topical route presents distinct advantages because there is low systemic clearance, minimum chance of drug interaction, relative patient tolerability and the feasibility of combination with various oral medications.
A variety of topical preparations have been investigated in CIPN. Previously, this gel has been reported to alleviate both mechanical allodynia and vulvodynia in an animal model of streptozotocin-induced diabetic neuropathic nociception and in the traumatic nerve injury model of neuropathic allodynia and hyperalgesia.
Both cisplatin and gabapentin were dissolved in normal saline.
The experimental procedures on animals were performed in compliance with the UK Animals Scientific Procedures Act 1986 and according to the rules and ethics set forth by the Institutional Ethical Committee. Cisplatin induced neuropathy treatment schedule Cisplatin-induced neuropathic nociception was established using four cisplatin intraperitoneal injections 3.
Before each cisplatin injection, hyperhydration was induced by the subcutaneous injection of 2.Neurontin gabapentin is an anti-epileptic drug, also called an anticonvulsant. It affects chemicals and nerves in the body that are involved in the cause of seizures and some.
An equivalent amount of control gel 1. Group 2: Cisplatin 3. Group 3: Saline 1.
Group 6: CG 1. Group 9: CG 1. Each filament was applied to the mid-plantar surface until it buckles and the nociceptive response was measured as the paw withdrawal threshold PWT. The static allodynia paradigm was determined at the end of each week.
Neuropathic paradigm of heat hypoalgesia The expression of cisplatin associated heat hypoalgesia was assessed in rat hind paws using a digital hot-plate apparatus Harvard apparatus, USA.