Concord Dependency Seminar: Tuesday July 25th 2006
Presenter: Dr Bridin Murnion, Clinical Supervisor, Division of Medicine, and Staff Specialist in Clinical Pharmacology at Royal North Shore Hospital.
Chair: Dr Richard Hallinan
Dr Murnion began by giving us the IASP (International Association for the Study of Pain) definition of pain: "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage." Pain is always a subjective experience, and for each person what is felt as "pain" is often learnt through experiences in early life. There are many people who are unable verbally to communicate their distress, and yet still need active treatment, including people with dementia, strokes, and intellectual disabilities.
Pain can be present despite no evidence of tissue damage, and we ought to avoid tying its definition to a noxious stimulus. The actual neurological activity produced by a stimulus is not pain until it is reported as such, and it is the subjective report of the patient that must guide our understanding and treatments.
Dr Murnion gave us the AAPM (American Academy of Pain Medicine) definitions of three terms that overlap the worlds of both pain management and dependency medicine "tolerance", "physical dependence" and "addiction":
- Tolerance: "A decrease in the effect of a drug over time so that a progressive increase in the amount of that drug is required to achieve the same effect. Tolerance develops to desired and undesired effects at different rates."
- Physical dependence: A physiological adaptation to a drug whereby abrupt discontinuation or reversal of the drug, or a sudden reduction in its dose, leads to a withdrawal (abstinence) syndrome. Withdrawal can be terminated by administration of the same or similar drug."
- Addiction: A disease that is characterised by aberrant drug-seeking and drug-taking behaviours that may include cravings, compulsive drug use, despite the risk of physical, social and psychological harm. While psychoactive drugs have an addiction liability, psychological, social and genetic factors may play a more important role in the development of addiction than exposure to the drug alone."
Addiction has a complex aetiology whereby a person's biological make-up interacts with psycho-social environment to have a strong bearing on whether use of a substance will lead to continued drug-seeking behaviours. The concept of addiction was contrasted to "pseudo-addiction" in which inappropriate drug-seeking behaviours are directly driven by a person's pain, and in fact resolve when that person is given adequate pain relief.
The similarity was noted to the DSM IV definition of dependence, which listing seven characteristics including tolerance and withdrawal, four of which need to be present to make a diagnosis.
Dr Murnion gave a detailed description of the neurobiology of pain. Pain signals pass from nociceptors in the end-organ tissues along the primary afferent nerve to the dorsal horn in the spinal cord, and thence up the spino-thalamic tract via the peri-aquaductal grey matter (PAG) to the sensory cortex, which identifies where the pain is located. Mu-opioid receptors are located in large numbers in the dorsal horn, and opiates binding here decrease the excitability of the cell membranes. Opiate tolerance occurs partly due to a decrease in the number of opiate receptors and also because of overactivity in the NMDA system (NMDA receptor is a subset of glutamate receptor). Tolerance and hyperalgesia occur via similar mechanisms, and Dr Murnion does not find the idea of opioid-induced hyperalgesia convincing: it is usually better explained by plain old opiate under-dosing.
We were advised to approach chronic pain using a biopsychosocial model: carefully formulate a diagnosis, taking note of any "red flags" that may indicate an aetiology like malignancy requiring a specific treatment as well as management of the pain per se. Details of all current and previous treatments should be obtained and we should develop a thorough understanding of the impact of the pain on the patient's life. Has it affected them in their vocation? What is the impact on their family life and interpersonal relationships? Are they depressed and/or anxious? What are their beliefs about the pain - do they think that it is "harming" their bodies and indicative of ongoing injury? Do they try and avoid activities in the belief that it will increase their pain? What do they expect the various treatments to achieve? Do they have any comorbidities, such as substance use?
We should set treatment goals, which may include a decrease in pain levels, but also psychosocial goals: optimising a person's ability to work, improving mood and personal relationships, and increasing their sense of meaning in their life. Planning will involve avoiding any unhelpful treatments and identifying risk factors for treatment failure.
Treatment options include opioids, paracetamol, NSAIDs, COX-ibs, anti-depressants (the most successful of which are tricyclics) and anti-epileptics. Other options include mobilisation, work rehabilitation, psychological treatments like CBT, and interventional techniques. The latter include dorsal column stimulators, regional nerve blocks and radio-frequency ablation of the medial branch nerves supplying facet joints in both the cervical and lumbo-sacral spines. Dorsal column stimulators have their best evidenced role in neuropathic pain, reflex sympathetic dystrophies, and intractable angina.
The research data on opiate use in chronic non-malignant pain is poor. There is some evidence that oxycodone may have a use in treatment of pain in the knee, back or neck secondary to osetoarthritis. Around 20% patients will suffer significant side effects, such as nausea and vomiting and particularly constipation and somnolence, worse at higher doses. Oxycodone also has some efficacy in treatment of diabetic neuropathy and post-herpetic neuralgia. Some epidemiological studies indicate that those on higher doses of oxycodone for chronic pain are more likely to have several comorbidities including alcohol and benzodiazepine dependence or a positive HIV status.
Up to 50% patients on methadone maintenance treatment (MMT) suffer from chronic pain. Patients on MMT who also have chronic pain are more likely to be on higher doses of methadone. There is some evidence that methadone is particularly effective in treating neuropathic pain. Some patients are reluctant to try methadone as a treatment for chronic pain because of its association with opioid dependency treatment.
Dr Murnion suggested that we adopt a set of "universal precautions", as described by Dr Doug Gourlay, before embarking on any treatment for chronic pain including the prescription opioids. There should be a careful psychological assessment done, including looking at the risk of addictive disorders (personal history, family history, maybe even a spot urine toxicology test). We should explore the patient's goals and define a treatment plan with the patients' consent, setting clear boundaries early on medication use. The use of opioids for chronic pain should always be seen as a 'trial' of opioid therapy, and pain and function should be continually assessed during treatment. Where there are concerns about a patient's psychiatric and drug and alcohol history, seeking support from pain specialists and clinics was encouraged.
Patients who are opioid dependent often require significantly higher doses of opioids to achieve pain control compared to opioid naive patients, and appear to have a higher incidence of hyperalgesia, being particularly sensitive to thermal stimuli like cold. Treating these patients requires not only an approach to pain management, but a knowledge of how to help avoid potential withdrawal syndromes.
Naltrexone, a competitive antagonist of opioids, and one of two widely used pharmacological treatments for alcohol dependency, is best ceased before any planned surgical procedure, to make management of post-operative discomfort open to opioid options. Its block is theoretically surmountable, and in situations where someone taking naltrexone presents in severe pain, one approach is to try and overcome the antagonism with high doses of opioids, although non-opioids may sometimes provide some response.
Buprenorphine is a partial agonist of opioids, and does have some (albeit limited) analgesic efficacy, so where minor procedures are undertaken on patients on buprenorphine maintenance, an increase in the dose of buprenorphine for pain control may suffice. However, with major surgical procedures and the likelihood of significant post-operative pain, a full opioid agonist should be substituted for buprenorphine pre-procedure.
In the second half of this seminar, Dr Murnion and Dr Hallinan presented case studies. The first was a 35 year old man with chronic low back pain ('CLBP') who developed iatrogenic opioid dependency with erratic and increasing opioid consumption, threatening behaviour in demanding opioids, and eventually, illicit opioid use. It was necessary to report him to the driver licensing authority. His management included attempted weaning off opioids with a ketamine infusion (as an NMDA antagonist), an unsuccessful trial of buprenorphine, his refusal to consider methadone on referral to a drug and alcohol service, and loss to follow up...
"Ellie", a 26 yo woman, was started on MMT after 2 years of increasing opioid seeking after a sinus operation and subsequent severe headaches with vomiting. During 3 years of MMT, her frequent headaches with vomiting meant she was often unable to keep down methadone, managed variously with metoclopramide and methadone intramuscularly, and methadone suppositories, also by medical centres at times with pethidine, morphine injections. At one hospital she developed lockjaw (dystonic reaction) after receiving prochloperazine followed by haloperidol for vomiting.
At another hospital where she presented after vomiting her methadone dose she was refused opioids and given metoclopramide and then droperidol injections to allow her to swallow aspirin: this was followed by a severe dystonic reaction to droperidol: which could have been foreseen from the known reaction to haloperidol.
Some of the issues were how iatrogenic dependency might have been prevented with "universal precautions"; how "opiophobia" in clinicians can lead to poor decisions; and relief of pain with vomiting in MMT.
Ken, 39 yo, was a pain clinic patient on MS Contin after accidents and injuries needing 47 different operations. With a past history of alcohol abuse, injecting drug use, cannabis, 40 cigs daily, he felt the pain clinic treated him as an addict, but he only used illicit drugs when his pain needs were not met. After his pain authority was revoked he started MMT, and only stopped using heroin when stabilised on 285mg/day, anti-inflammatory medications and an antidepressant..
Over years of MMT, he frequently used alcohol up to 200g/day, and intermittently used injected stimulants, benzodiazepines " by the handful", and large amounts of cannabis, especially when he tried to reduce his methadone. He also had low sex drive, had lost muscle, put on fat, and complained of growing breasts, and was found to have low testosterone (probably due to the methadone). He was frustrated being 'trapped' on methadone.
Issues discussed were the need for a thorough reappraisal of his orthopaedic issues, looking at his psychosocial situation, and getting a sympathetic pain clinic review - it was noted that a pain clinic could hardly be blamed for treating this man like an addict, as he was surely one! It was asked "What is the problem, actually?" - maybe he ought simply to accept MMT for life. Finally it was suggested that androgen replacement might help give him more strength, resilience, better mood and improved pain tolerance.
This application of theory to "real" cases concluded an excellent seminar on the interface between dependency and pain management medicine.