Vivek Mehta

Controversies and advances in non-steroidal anti-inflammatory drug (NSAID) analgesia in chronic pain management

Chronic pain can lead to significant disability with social and economic implications in the community. Traditional non-steroidal anti-inflammatory drugs (NSAIDs) have been part of the management of chronic pain. The risk of adverse events with traditional NSAIDs has led to the development of alternative therapeutic options. Differential blockade of the enzymes involved in pain and inflammation can offer therapeutic options without the gastrointestinal side effects. However, this may be at the expense of other major cardiovascular side effects. Pain pathways that involve peripheral transmission may be altered by local application of analgesia to the skin overlying the painful area. Recent guidelines for osteoarthritis treatment from the National Institute for Health and Clinical Excellence highlight the importance of topical NSAIDs in the armamentarium of pain management. NSAID combination drugs with gastric protection have provided alternatives to traditional NSAIDs, but the long term sequelae are unknown.

Intravenous Parecoxib Rapidly Leads to COX-2 Inhibitory Concentration of Valdecoxib in the Central Nervous System

Evidence in animal studies supports widespread induction of cyclooxygenase‐2 (COX‐2) in the central nervous system (CNS) following tissue injury, probably mediated by cytokines, transducing the signal across the blood–brain barrier. CNS COX‐2 blockade is a possible therapeutic target for drugs that are able to reach adequate CNS levels and abolish the prostaglandin E2‐induced central sensitization. This human pharmacokinetic study investigated valdecoxib cerebrospinal fluid (CSF) and plasma concentrations over time in 37 patients following 40 mg of single‐dose intravenous parecoxib. High‐performance liquid chromatography/tandem mass spectrometry analysis was performed. Valdecoxib was first detectable in the CSF at 15 min postdosing, increased rapidly until 50 min, and thereafter remained between 6 and 14 ng/ml. This is the first human study demonstrating CNS COX‐2 inhibitor penetration as early as 15 min. CSF valdecoxib concentration rapidly reached in vitro IC50 (inhibitory concentration 50) (1.57 ng/ml) by 17 min and remained consistently higher thereafter.

Pain assessment and management in medical wards: an area of unmet need

Background Acute Pain Services (APS) were introduced primarily to improve postoperative pain management. Although pain is similar in prevalence and severity in medical and surgical wards, its assessment and management in non-surgical patients often receives less attention and resources. Objective To investigate the extent of APS involvement on medical wards and obtain perceptions of deficiencies. Method A questionnaire was mailed to APS leads in 287 UK NHS hospitals; 229 questionnaires were returned (79.8% response). Results Only 36 (16%) of the 225 hospitals with medical wards reported routine APS involvement. Pain scores were not recorded in 75 (33%) hospitals, 11 (5%) denied knowledge about assessments being conducted, and 185 (82.2%) respondents felt that pain management on medical wards was inadequate. Conclusions Perceived lack of training and awareness of healthcare staff were highly ranked contributing factors, and this was attributed to inadequate funding. This study highlights the scope for improvement of pain control in medical patients, with benefits from reduced morbidity and faster recovery.

Recent advances in opioid prescription for chronic non-cancer pain

Chronic pain is pain that persists past the normal time of healing, and is seen as a common problem with a significant socioeconomic impact. Pharmacological management for chronic non-cancer pain also involves the prescription of opioids, with the aim of an improved quality of life for the patient. New guidelines have been published to aid prescribing clinicians improve opioid safety and patient care, and include recommendations on when to refer patients to a pain specialist. In recent years there has been a rapid increase in opioid prescription in the UK and USA, prompting further concern regarding opioid abuse and side effects. Opioid use may also result in physical dependence and tolerance. Earlier recognition and diagnosis of unwanted effects of long term opioid use is needed, such as opioid induced suppression of the hypothalamic–pituitary–gonadal axis, and opioid induced immunosuppression. Patients may themselves discontinue opioids, however, due to minor side effects. Recent advances in opioid prescription include the increasing use of transdermal preparations and extended release, oral, once daily preparations. New formulations of existing drugs have been developed, as well as a new chemical entity. Abuse deterrent formulations and delivery systems may prevent the artificial acceleration of drug delivery and reduce the potential for opioid addiction. Overdose concerns and the potential for fatal overdose may necessitate mandatory training for all clinicians who prescribe opioids. Despite the widespread use of opioids in the management of chronic non-cancer pain, significant research gaps remain. An improvement in the evidence base for its prescription is required.

Pulsed radio frequency: a non-neurodestructive therapy in pain management

Purpose of reviewTo appraise and discuss the current available evidence on pulsed radio frequency (PRF), with an emphasis on published randomized controlled clinical trials. Recent findingsPulsed radio frequency is a minimally invasive procedure used to treat a wide variety of chronic pain conditions. It is considered to be a safe and effective pain intervention with minimal side effects when performed by an experienced clinician with careful patient selection. Its mechanism of action is thought to be via neuromodulation, as ‘pulses’ of electric current are created at the electrode tip without a significant rise in temperature. Painful conditions successfully treated with PRF include chronic cervical radicular pain, trigeminal neuralgia, chronic shoulder pain and chronic low back pain. SummaryAt present very few well designed randomized controlled trials have been carried out on patients comparing PRF to another technique. Further scientific research and clinical trials are required to confirm whether PRF has a significant role in the future of chronic pain management.

A comparison of the respiratory effects of oxycodone versus morphine: a randomised, double-blind, placebo-controlled investigation*

Oxycodone’s respiratory profile (particularly the extent of respiratory depression in comparison to morphine) remains to be fully characterised in the peri‐operative period. We randomly assigned ASA 1‐2 adults for elective surgery under general anaesthesia to receive saline, morphine 0.1 mg.kg−1, or oxycodone 0.05 mg.kg−1, 0.1 mg.kg−1, or 0.2 mg.kg−1. Results were obtained from six patients in the saline group, 12 patients in the groups receiving morphine 0.1 mg.kg−1, oxycodone 0.05 mg.kg−1 and 0.1 mg.kg−1, and from 10 patients who received oxycodone 0.2 mg.kg−1. Patients were breathing spontaneously and minute ventilation monitored with a wet wedge spirometer for 30 min. All active groups demonstrated significant respiratory depression compared to saline (p < 0.0001 for all groups). The mean (SD) reduction in minute volume from baseline was 22.6% (10.4%) for the morphine 0.1 group and 53.3% (27.2%), 74.4% (12.9%) and 88.6% (13.5%) for the oxycodone 0.05, 0.1 and 0.2 groups, respectively, with significant dose dependent differences between oxycodone groups (p = 0.0007). The extent and speed of onset of oxycodone induced respiratory depression was dose dependent and greater than an equivalent dose of morphine.

Tapentadol--the evidence so far.

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First evidence of the conversion of paracetamol to AM404 in human cerebrospinal fluid

Paracetamol is arguably the most commonly used analgesic and antipyretic drug worldwide, however its mechanism of action is still not fully established. It has been shown to exert effects through multiple pathways, some actions suggested to be mediated via N-arachidonoylphenolamine (AM404). AM404, formed through conjugation of paracetamol-derived p-aminophenol with arachidonic acid in the brain, is an activator of the capsaicin receptor, TRPV1, and inhibits the reuptake of the endocannabinoid, anandamide, into postsynaptic neurons, as well as inhibiting synthesis of PGE2 by COX-2. However, the presence of AM404 in the central nervous system following administration of paracetamol has not yet been demonstrated in humans. Cerebrospinal fluid (CSF) and blood were collected from 26 adult male patients between 10 and 211 minutes following intravenous administration of 1 g of paracetamol. Paracetamol was measured by high-performance liquid chromatography with UV detection. AM404 was measured by liquid chromatography-tandem mass spectrometry. AM404 was detected in 17 of the 26 evaluable CSF samples at 5–40 nmol⋅L−1. Paracetamol was measurable in CSF within 10 minutes, with a maximum measured concentration of 60 μmol⋅L−1 at 206 minutes. This study is the first to report on the presence of AM404 in human CSF following paracetamol administration. This may represent an important finding in our understanding of paracetamol’s mechanism of action, although measured concentrations were far below the previously documented IC50 for this metabolite.

‘Simplicity’ radiofrequency neurotomy of sacroiliac joint: a real life 1-year follow-up UK data

Background: Sacroiliac joint (SIJ) pain is considered to be the third most common cause of low back pain with the prevalence of 13–25% in all low back pain patients. Its diagnosis and treatment remain a challenge with the poor evidence base for interventional procedures. Patients with SIJ pain experience a low quality of life, worse than some of the chronic health conditions. Simplicity radiofrequency (RF) neurotomy is a novel technique which tackles some of the problems faced by conventional RF neurotomy and may offer better results in managing pain arising from SIJ. Aim: The purpose of this retrospective review of practice was to look into the effectiveness of Simplicity RF neurotomy in terms of pain relief, quality of health improvement in patients suffering from SIJ pain and complications associated with the procedure. Methodology: Retrospective review of the patients undergoing Simplicity RF neurotomy at a tertiary hospital (April 2012 to June 2013). Pain scores and responses to SF (Short Form) 12 questionnaire before and at 12 months after treatment were compared using the Wilcoxon signed-rank test. Results: Out of 26 patients, 16 were considered for analysis. There was statistically significant reduction in both mean pain score (Numerical Rating Scale, NRS from 8.8 pre-intervention to 4.3 post-intervention) and median pain score (NRS from 9 pre-intervention to 5 post-intervention) with a p-value of <0.001 at 12 months. Reduction in the inter-quartile range of pain score was observed from 8–10 to 2.25–6 (p-value of <0.001). Global health as per SF12 scores showed statistically significant improvement, except in some of the psychological subcategories. The procedure-related pain was the only complication noted. Conclusion: From our data, we can conclude that Simplicity RF neurotomy of lateral branches of S1-S3 along with conventional RF denervation of L5 dorsal ramus may improve pain scores and many components of global health in carefully selected patients.

Acute Pain Management in Opioid Dependent Patients.

• • Acute pain management remains a challenge in opioid dependent patients, and it has been recognised that these patients are commonly under-treated. • Chronic opioid exposure leads to widespread adaptations both at cellular and synaptic level. • Physical dependence is a neuropharmacological phenomenon as a result of neuroadaptation and neuroplasticity, in contrast to addiction that is both neuropharmacological and behavioural. • While providing the patients pre-existing opioid requirement, the acute pain episode should be managed using additional multimodal analgesia: non-opioid medications in combination with local anaesthetic techniques and as required, short-acting opioid titrated to effect. • Patients on long term buprenorphine and methadone with acute pain episode should be continued with their maintenance therapy and an additional short-acting opioid analgesic titrated to achieve therapeutic effect.