Evidence and consensus recommendations for the pharmacological management of pain in India

Abstract

Despite enormous progress in the field of pain management over the recent years, pain continues to be a highly prevalent medical condition worldwide. In the developing countries, pain is often an undertreated and neglected aspect of treatment. Awareness issues and several misconceptions associated with the use of analgesics, fear of adverse events - particularly with opioids and surgical methods of analgesia - are major factors contributing to suboptimal treatment of pain. Untreated pain, as a consequence, is associated with disability, loss of income, unemployment and considerable mortality; besides contributing majorly to the economic burden on the society and the health care system in general. Available guidelines suggest that a strategic treatment approach may be helpful for physicians in managing pain in real-world settings. The aim of this manuscript is to propose treatment recommendations for the management of different types of pain, based on the available evidence. Evidence search was performed by using MEDLINE (by PubMed) and Cochrane databases. The types of articles included in this review were based on randomized control studies, case-control or cohort studies, prospective and retrospective studies, systematic reviews, meta-analyses, clinical practice guidelines and evidence-based consensus recommendations. Articles were reviewed by a multidisciplinary expert panel and recommendations were developed. A stepwise treatment algorithm-based approach based on a careful diagnosis and evaluation of the underlying disease, associated comorbidities and type/duration of pain is proposed to assist general practitioners, physicians and pain specialists in clinical decision making.

Keywords: clinical practice guidelines; consensus recommendations; expert opinion; pain management; treatment algorithm.

Figure 1

Mechanism of peripheral versus central sensitization. Notes: (A) Peripheral sensitization and (B) central sensitization. Activation of peripheral nociceptors on the skin in response to stimuli, such as heat, injury or mechanical pressure, initiates the release of chemical mediators at the site of injury (peripheral sensitization). Persistent pain or inflammation causes activation and repetitive firing in afferent C-fiber nociceptors, which triggers the release of excitatory neurotransmitter glutamate in the synapse of the dorsal horn (central sensitization). This is accompanied by the release of substance P, BDNF and neurokinins, which causes persistent depolarization of the cell membrane. Additionally, activation of AMPA or NMDA receptors by glutamate stimulates the microglia and subsequently induces the release of cyclooxygenase enzymes 1 and 2, nitric oxide and other proinflammatory mediators (TNF-α, IL-1, IL-6). Abbreviations: AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; ATP, adenosine triphosphate; ASIC, acid-sensing ion channels; BDNF, brain-derived neurotropic factor; 5-HT, 5-hydroxytryptamine; IL, interleukin; NMDA, N-methyl-d-aspartate receptor; NGF, nerve growth factor; PG, prostaglandin; NK₁, neurokinin-1; TNF, tumor necrosis factor; TrkB, tyrosine receptor kinase B; TRPV, transient receptor potential vanilloid receptor.

Figure 2

Therapeutic modulation of the pain-processing pathway. Abbreviations: NMDA, N-methyl-d-aspartate receptor; NSAID, nonsteroidal anti-inflammatory drug.

Figure 3

Pain algorithm. Notes: ^aAvoid in age >60 years, cardiovascular/GI/renal comorbidities; ^bavoid long-term therapy in opioid dependence/tolerance; ^cfirst-line therapy for acute NP, NP due to cancer, acute exacerbations of severe NP as well as when titrating one of the first-line medications, if prompt relief of pain is required. Abbreviations: GI, gastrointestinal; NP, neuropathic pain; NSAID, nonsteroidal anti-inflammatory drug; SNRI, serotonin–norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant.