Neuropathic pain is a disease or impairment of somatosensory nervous system, characterized by spontaneous and evoked pain, affecting 2% – 3% of the general population.1-3 Some epidemiological studies have suggested its prevalence to lie between
6.9 to 10%.4 Nevertheless, it is still an underdiagnosed and undertreated disorder across the globe.5 There are several etiologic causes of neuropathic pain. These comprise infectious agents, metabolic diseases, neurodegenerative diseases, and physical trauma (figure 1).6 Majority of patients with symptoms of neuropathic pain are managed in primary care, with only a minority being referred for specialist clinical evaluation and diagnoses.4 The fundamental research in the field of neuropathic pain enables the identification ofdifferentpathophysiologicalmechanisms, andclinical evaluation of symptoms may assist in determining the mechanisms involved in specific neuropathic pain disorders.7
Recent studies specify that peripheral neuropathic pain is provoked via a focal inflammatory process rather than axonal destruction. This process also seems to involve mRNA regulation of fast sodium channels, which produce ectopic discharges and are presumably responsible for pain generation. Additionally, the entire neuroaxis endures neuroplastic changes due to peripheral nerve injury.8 Researchers suggest that all patients with neuropathic pain are associated with poor general health compared to those with other severe chronic diseases.9 Therefore, it is imperative to achieve an accurate diagnosis which can lay the foundation for appropriate management. Usually, an interdisciplinary approach, focusing primarily on pharmacological therapy is recommended for patients with neuropathic pain.7
Several treatment options have been studied for the management of neuropathic pain. However, literature is still lacking in the practical aspects of patient management. According to the International Association for the Study of Pain (IASP) and Neuropathic Pain Special Interest Group (NeuPSIG), pharmacotherapy is considered as the gold standard for the management of neuropathic pain.10,11 Both IASP and NeuPSIG have promoted the development of evidence-based guidelines for the pharmacological management of the condition. As per the guidelines the calcium channel a2-d ligand has been suggested
as the first-line agent. 12 Pregabalin is a potent a2-d
ligand which binds in a state-dependent manner to the a2-d sub-unit of voltage-gated calcium channels of “over-excited” pre-synaptic neurons, thus changing the conformation of the channel and dropping the release
of excitatory neurotransmitters such as glutamate and substance P. This subsequent reduced stimulation of post-synaptic neurons is considered to be responsible for its anxiolytic, anticonvulsant, and analgesic effects.13Severalresearchesprovidesevidenceinsupport of pregabalin efficacy for both central and peripheral neuropathic pain. Besides, pain relief, maintenance of nerve function and regeneration of myelin sheath is also mandatory for adequate management of neuropathic pain.14Methylcobalamin is an activated form of vitamin B12, aids in myelin sheath regeneration and restoration of nerve function in neuropathic pain.15
A combination of pregabalin and methylcobalamin hassynergisticeffectonthemanagementofneuropathic pain. A prospective study14 was conducted to evaluate the efficacy and safety of a fixed-dose combination of sustained-release pregabalin and methylcobalamin in reducing neuropathic pain. The patients were allocated to receive a fixed dose combination of 75 or 150 mg sustained-release pregabalin combined with 1500 mcg immediate release methylcobalamin, depending upon the clinical requirement. The data was collected for pain reduction and other positive and negative symptoms allied with neuropathy, including hyperesthesia, paresthesia, numbness, burning sensation, muscle weakness, sleep disturbances, and impairment of movement.
The intensity of pain was measured on a ten-point visual analog scale (VAS). Moreover, the safety of the drug was also assessed during the study period. The results revealed that the overall reduction in mean VAS score was 72.3%. Moreover, the positive and negative symptoms of peripheral neuropathy were considerably improved in >50% of patients within 2 weeks. The overall efficacy and tolerability reported was 95% (figure 2). Similar results were shown in another meta-analysis of studies16 which showed that clinical efficacy and tolerability with combination therapy of pregabalin (75 mg) and methylcobalamin (750 µg) in neuropathic pain was 88.11% and 81.48%, respectively. Furthermore, the combination therapy of pregabalin/methylcobalamin is proved to be more efficacious than pregabalin monotherapy. A study17 was performed to assess the efficacy and safety of pregabalin/ methylcobalamin compared to pregabalin monotherapy for the treatment of neuropathic pain. A total of 32 adult patients were randomized to receive either pregabalin 75 mg and methylcobalamin 750 μg combination, or pregabalin 75 mg for a period of 12 weeks. The results revealed that methylcobalamin and pregabalin combination provided more pain relief and improved sleep interference compared to pregabalin monotherapy. Moreover, the addition of methylcobalamin to pregabalin improved the nerve function also.
Hence, the researchers concluded that combination therapy of pregabalin and methylcobalamin is an effective and safe option for the management of neuropathic pain.
Neuropathic pain is an impairment of somatosensory nervous system and is still an underdiagnosed and undertreated disorder worldwide. Patients with neuropathicpainareassociatedwithpoorgeneralhealth. Thereby, their accurate diagnosis and management is imperative. Pregabalin is the first-line agent for the management of neuropathic pain. Its combination along with methylcobalamin has synergistic effect on the management of neuropathic pain. Information available from several studies provides compelling evidence in favor of their efficacy and safety for the treatment of the condition.