Please use this identifier to cite or link to this item:
Title: Pharmacological Efficacy of Systemic and Topical 6-Methoxyflavone and Bacopa monnieri in the Rodent Neuropathic Nociceptive Paradigms
Authors: Shahid, Muhammad
Keywords: Pharmacy
Issue Date: 2019
Publisher: University of Peshawar, Peshawar.
Abstract: Neuropathic pain occurs due to a lesion or disease process affecting the somatosensory system. This pain is usually presented as an evoked response to non-painful stimuli (allodynia) and an exaggerated response to potentially painful stimuli (hyperalgesia). Despite rapid advancement of neuroscience and modern techniques related to drug design, effective drugs to mitigate the painful symptoms of neuropathy are still lacking. Systemic pharmacotherapy is currently regarded as the mainstay treatment and guidelines suggest offering a choice of gabapentin, pregabalin, amitriptyline, duloxetine, and tramadol. Unfortunately, the clinical effectiveness of these systemic agents can be limited by the extent of pain relief provided and the occurrence of significant side-effects. These limitations may be curtailed by investigating additional safe and effective agents and by localized therapy. In the present study, the flavonoid 6-methoxyflavone and a standardized extract of Bacopa monnieri (L.) Pennell (family: Scrophulariaceae), a widely reputed nootropic plant, were investigated via the systemic and topical routes for prospective neuropathic pain attenuating efficacy in the well-established rat models of chronic constriction injury of the sciatic nerve (CCI), cisplatin and streptozotocin induced neuropathic nociception. The neuropathic paradigms measured were static and dynamic mechanical allodynia (paw withdrawal threshold [PWT] to von Frey monofilaments and latency [PWL] to light brushing with a cotton bud), cold allodynia (paw withdrawal duration [PWD] to an acetone drop), heat hyperalgesia and hypoalgesia (increase and decrease PWL to a heat stimulus) and mechano-hyperalgesia (PWD to pin-prick), static and dynamic mechanical vulvodynia (flinching response threshold to the von Frey filaments pressure [FRT] and latency to light brushing [FRL] of the vulvar region). Additionally, any effect on the neuronal function produced after systemic and topical treatments was assessed using the paradigms of open field, rotarod, and footprint pattern analysis. For the systemic treatment, the antinociceptive doses for 6-methoxyflavone were 25, 50, and 75 mg/kg, while those of B. monnieri were 40 and 80 mg/kg. Gabapentin at 75 mg/kg was used as positive control. Topical gels of 6-methoxyflavone and B. monnieri were prepared in concentrations of 6% and 10% in relation to the clinically effective gabapentin gel. The relevant neuropathic nociceptive paradigms were successfully expressed in the operated hindpaw after placement of four loose ligatures around the sciatic nerve (days 3-21) and in both the hindpaws during the four weekly cisplatin injections and after the single injection of streptozotocin (days 7-28). These were exemplified as a significant decreased PWT to von Frey monofilaments, decreased PWL to cotton bud stroking and heat as well as an increased PWL to heat (cisplatin only), increased PWD to a drop of acetone and pin-prick, and decreased FRT to von Frey filaments and FRL to cotton bud (streptozotocin only). The daily systemic doses of 6-methoxyflavone and B. monnieri significantly attenuated the overall maintenance of mechanical and cold allodynia, mechanical and thermal hyperalgesia, heat hypoalgesia, and tactile vulvodynia during the expression days. Similarly, gabapentin treatment also afforded an analogous beneficial behavioral profile. The three times daily applications of the topical gels of 6-methoxyflavone and B. monnieri ipsilaterally but not contralaterally alleviated the neuropathic aberrations in the CCI induced nociception model and also in the cisplatin and streptozotocin induced polyneuropathy in both hindpaws. Accordingly, daily application of gabapentin gel on the mid-plantar area also showed a comparable suppression of neuropathic expression. However, the antinociceptive actions of gabapentin via the systemic route were associated with immobility along with motor impairment exemplified by a significant decrease in rotarod endurance latency and a deficit in the uniformity of step alternation. In Summary 3 contrast, the systemic and topical 6-methoxyflavone and B. monnieri were devoid of these unwanted effects and in fact the systemic treatments corrected these neuronal dysfunctions specifically associated with cisplatin and streptozotocin neuropathic models. The gabapentin 10% gel also afforded desirable neuropathic pain alleviating effects devoid of unwanted systemic side-effects, thereby indicating local antinociceptive actions for the topical gels. These outcomes suggest that systemic treatment with 6-methoxyflavone and B. monnieri afforded desirable neuropathic pain alleviating propensities when tested against an extensive range of nociceptive stimulus modalities without producing any gabapentin-like unwanted motoric side-effects. These findings also disclosed an expedient pharmacological validation of the effectiveness of topical route in the management of neuropathic pain. The systemic and topical 6-methoxyflavone and Bacopa monnieri can be used as an adjuvant therapy for pain conditions including neuropathic pain afflicted with allodynia and hyperalgesia and/or heat hypoalgesia as well as for diabetes associated vulvar pain. Further studies are advocated in other animal models along with clinical studies with regard to certain neuropathic pain syndromes in addition to elaborate pharmacodynamic and pharmacokinetic evaluation.
Gov't Doc #: 18891
Appears in Collections:PhD Thesis of All Public / Private Sector Universities / DAIs.

Files in This Item:
File Description SizeFormat 
Complete thesis29_M Shahid_PhD_Pharmacy_Reports7.pdf17.89 MBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.