Pain Associated with Chronic Narcotic Dependence


states. Spinal dorsal horn glia can be activated in response to a number of factors that include inflammation, infection, opiates, peripheral injury and in response to central signals.23


In an elegant series of recently


published studies, Agostini et al. present robust evidence that spinal microglial activation mediates morphine-induced visceral hypersensitivity.24


In a rodent model, these authors demonstrated the development of visceral hyperalgesia to colorectal distension following prolonged administration of morphine. They subsequently observed that morphine co-administration with minocycline, a microglia inhibitor, ameliorated this aforementioned hypersensitivity.


In addition, it is fascinating to note that spinal glial cells express receptors for a number of pro-inflammatory cytokines such as interleukin-1 (IL-1), IL-6 and tumour necrosis factor-α (TNF-α), as well as having the ability when activated to release mediators such as NO, prostaglandins and excitatory amino acids, all of which can enhance pain transmission and further drive neuropathic pain.25


Exogenous


opiates, binding directly to the mu receptor, cause the activation of glia with the concomitant release of pro-inflammatory cytokines, thereby accelerating this process. Glia, in response to the release of inflammatory mediators, may activate neurons through a novel chemokine (known as fractalkine) mediated mechanism.26


These


mechanisms provide important evidence for the concept of opiate- induced hyperalgesia. Translational pharmacological studies are now warranted to support these proposed mechanisms and their targeted effects in humans.


Management of Narcotic Bowel Syndrome There is no consensus regarding the optimal medical management of NBS, but many authorities regard the physician–patient relationship to be a critical factor in achieving a successful outcome. Both of these stakeholder groups approach the management of NBS with contrasting agendas. The physician’s agenda is to withdraw the counterproductive opiate therapy in order to potentially improve the patient’s symptoms and HRQoL. However, from the patient’s perspective opiate withdrawal, their tapering or their restriction may bring into question perceived unease regarding the physician’s appreciation of symptom legitimacy in addition to potential issues regarding addiction. In this respect, the physician must actively acknowledge the validity of the patient’s symptoms and provide information through intensive dialogue. We suggest that such information needs to include basic physiological and anatomical facts about opiate-induced bowel dysfunction as well as provide a rational explanation for opiate withdrawal. The physician must engage and respond to the patient’s concerns and provide reassurance wherever possible. The patient must display a degree of willingness and determination to succeed within a set of realistic and achievable goals. Treatment plans should be discussed with other stakeholders such as allied healthcare professionals and the patient’s family members. Put simply, management is considerably more complicated than following a simple opiate withdrawal protocol. Whereas the preparatory phase for treatment may be undertaken as an outpatient, we advocate that the opiate withdrawal programme be undertaken in secondary or tertiary care under the supervision of an experienced specialist.


Treatment Modalities


The specific goals of treatment are two-fold: first, by commencing pharmacotherapy, to minimise the short-term withdrawal effects of opiates; and second, to effectively treat psychological co-morbidities while achieving pain control for the underlying pathology. The


EUROPEAN GASTROENTEROLOGY & HEPATOLOGY REVIEW Benzodiazepines


Medium- and long-acting benzodiazepines, such as lorazapam or clonzapam, may be helpful in reducing patient anxiety, which is often associated with the acute phase of opiate withdrawal, and may be


119


Figure 1: Summary of the Treatments for Opiate Withdrawal in Narcotic Bowel Syndrome


Start Opiate withdrawal


Substitute opiate with regular medium to long opiate aiming for 10–33% dose reduction per day, e.g. methadone.


Antidepressants


Commenced prior to opiate withdrawal and continued after withdrawal completed, e.g. amitriptylline, duloxetine.


Continue indefinitely 7–10 days


Benzodiazepine cover


Regular benzodiazpine during withdrawal phase, tapered off after opiate withdrawal is completed, e.g. lorazepam.


Clonidine


Used during acute withdrawal for treatments of sympathetically mediated withdrawal symptoms. May have long-term analgesia and anti-diarrhoeal effects.


Other treatments


Other treatments that may be considered specific treatment of constipation and psychological treatments, including cognitive behavioural therapy.


10–14 days


The diagnosis of narcotic bowel syndrome needs to be made and a therapeutic doctor– patient relationship established before treatment can commence. Source: Farmer AD and Aziz Q, Gastrointestinal manifestation of opiate therapy. In: Hakim AJ, Keer RJ, Grahame R (eds), Hypermobility, Fibromyalgia and Chronic Pain, Churchill Livingstone, 2010.


We would agree with Grunkemeier et al. when they suggest switching the offending opiate for an equivalent dose of a medium- to long-acting opioid, such as methadone, and then decreasing the dose of this by 10–33% per day. An equally divided daily dose should be used so as to limit large variations in plasma concentrations, thereby avoiding rebound pain during trough levels.1


Concomitant medications


such as antidepressants, benzodiazepines and clonidine can be commenced during the opiate withdrawal phase, for variable periods, to treat co-existing anxiety, psychological co-morbidity and provide long-term central analgesia. Figure 1 summarises a suggested pharmacological approach to opiate withdrawal.


Antidepressants


Antidepressants should be commenced prior to opiate withdrawal and may be continued indefinitely, although clinical benefit may not be tangible for a number of weeks. Tricyclic antidepressants, e.g. amtriptylline, are the treatment of choice due to their beneficial noradrengerically mediated analgesic effects. However, tolerance is limited often by anticholinergic (constipation, blurred vision, dry mouth) and histaminergic (somnolence) side effects. Alternatives include the serotonin–noradrenergic reuptake inhibitors, such as duloxetine, which provide long-term analgesia and antidepressant activity with improved GI tolerance.


time-frame that is needed for a successful opiate withdrawal programme is extremely variable but those who have had longer durations and higher doses of opiates often require a more prolonged period of graded withdrawal. It is our clinical experience, and that of others, that opiate withdrawal regimens take between five and 14 days.1


Continue indefinitely


Can be tapered or continued indefinitely


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