CLINICAL SCIENCE


neuropathic pain. Ivabradine does not cross the blood-brain barrier so it has little likelihood of the CNS-related side-effects commonly associated with gabapentin. Ivabradine appears to inhibit the perception of pain by blocking HCN-dependent repetitive firing in peripheral nociceptive neurons. This observation questions the involvement of the CNS in the development of neuropathic pain. Unfortunately, ivabradine causes bradycardia and, as such, is not an ideal agent for treatment. Research supported by the Wellcome


Trust is searching for HCN-2 blocking agents that do not cause bradycardia and that act peripherally, thus avoiding CNS side-effects. This work suggests that peripheral nervous system damage as the cause of neuropathic pain, and questions the extent of involvement of the CNS in neuropathic pain.


Self-efficacious activities, such as yoga, also play an important role in reducing pain.


of a single amputee performing mirror therapy. Pre-amputation mirror therapy may be helpful in development of post-surgical symptoms but studies are preliminary.


The problem with opioids Dr Leonard B Kamen (Physical Medicine and Rehabilitation, Moss Rehab Hospital, Temple University Hospital Department of Physical Medicine and Rehabilitation, Philadelphia PA, USA) spoke on alternatives to mu opioids in the biopsychosocial rehabilitation of chronic pain. Of the three family members of opioid receptors (mu, delta and kappa), Dr Kamen focused on the mu opioid receptors (MOR) that produce powerful analgesic effects in the central nervous system (CNS) but also create potentially problematic effects including euphoria, impaired cognition and motor function, as well as physical dependence. Mu opioids with the greatest abuse potential include morphine, heroin, methadone, oxycodone and hydromorphone. Dr Kamen stated he is not what some might refer to as an ‘opio-phobe’ but believes these substances are too often prescribed as a quick fix for complex problems. The combined problem of euphoria and


dependence, along with policies that foster over-prescribing of this class of opioid (particularly in the USA), can be dealt with better by using alternate analgesics, such as the opioid agonist-antagonist buprenorphine, and incorporating biopsychosocial avenues of pain management. Psychological interventions (ie cognitive behavioural therapy, meditation and hypnosis) alter pain perception and promote favourable neuroplastic changes in the CNS. Self-efficacious activities (eg yoga and breathing exercises) and passive therapies (eg manipulation and massage) also play an important role in reducing pain. Exercise and social support systems


promote brain health in a manner that similarly benefits the pain experience.


THE BIOMEDICAL SCIENTIST MAY 2016


‘It is suggested that antibiotics may not only combat infection but may also change the intestinal flora, which in turn moderates inflammation’


Dr Kamen stressed that a multidisciplinary, multimodal model of pain management avoids the dopaminergic rewards, resulting euphoria and drug-seeking behaviour that are a hallmark of mu opioid abuse.


Neuropathic pain Professor Peter McNaughton (King’s College London) discussed the likelihood that many long-term, unresolved pain conditions, as diverse as low back pain, post-herpetic neuralgia and diabetic neuropathy, all have neuropathic elements. Another commonality of these types of condition is that they are poorly managed with current treatments. Hypothetically, neuropathic pain is thought to be the result of repetitive neural firing in nociceptive (pain-sensitive) sensory nerve fibres but the specific pathogenesis of this phenomenon is unclear. Professor McNaughton stated that


hyperpolarisation-activated cyclic nucleotide-gated-2 (HCN-2) ion channels are expressed in nociceptors. Inflammatory mediators, such as PGE2, promote firing of nociceptive sensory neurons by downstream targeting of HCN-2 ion channels, thus implicating HCN-2 ion channels in both inflammatory and neuropathic pain conditions. Experimental genetic deletion of HCN-2 receptors in mice abolishes all modes of neuropathic pain. Early studies suggest the


pharmacological agent ivabradine, which blocks HCN-1, -2, -3 and -4 ion channels, is as effective as gabapentin in suppressing


Moderating inflammation Dr Ole Kudsk Jensen (Spine Centre, Diagnostic Centre, Regional Hospital Silkeborg, Denmark) presented evidence from multiple published studies in which he and colleagues developed a validated predictive model that could identify sick- listed low back pain (LBP) patients with low-, intermediate- and high-risk for not returning to work. The prediction model included pain intensity, side-flexion, bodily distress and resource issues. Furthermore, risk factors for continuing pain and disability were presented. In a subgroup, magnetic resonance imaging (MRI) of the lumbar spine was available. When adjusting for the prediction model and other risk factors, only type 1 Modic changes were a risk factor for not returning to work and for continuing pain and disability. Other degenerative manifestations, including disc herniation, were not associated with the prognosis. Thus, type 1 Modic changes seem to be a particularly important prognostic factor in sick-listed/work-disabled patients in contrast to other degenerative manifestations seen on imaging not associated with clinical outcomes. Dr Jensen concluded his presentation with the tantalising notion that antibiotic therapy may benefit patients with chronic low back pain and type 1 Modic changes as shown in a randomised Danish study. He suggested, however, that antibiotics may not be combating an infection but rather may change the intestinal flora, which in turn moderates inflammation. He is beginning a trial to test this hypothesis by treating patients with lactic acid bacteria supplementation.


Dr Robb Russell is Director, Spine Care, SCU Health System, Southern California University of Health Sciences, and Attending Chiropractic Doctor, PM&R Services, VA Medical Center, West Los Angeles CA, USA. The Science of Pain and its Management 2016 is schedule to take place on 6–8 December 2016 (www.lifescienceevents.com/pain2016).


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©Pete Saloutos/Fotolia


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