Opioids for chronic pain in the prison population

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Opioids for chronic pain in the prison
population good or bad?

• Dr Lesley Colvin
• Consultant/ Hon Reader in Anaesthesia Pain
  Medicine
• University of Edinburgh

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Opioids for severe chronic pain?
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Pain and disability
Great news Mr W youll still be able to play
the harmonica!
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Evidence for opioid use in chronic pain

• Key recommendations
• Strong opioids should be considered for chronic
  low back pain or osteoarthritis, and only
  continued if there is ongoing pain relief (B)
•  Specialist referral or advice if
• concerns about rapid-dose escalation with
  continued unacceptable pain relief
• or
• gt180 mg/day morphine equivalent dose is required
  (D)
• How do these apply in the context of substance
  misuse and in the prison population?

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Opioids long term adverse effects

• Central Nervous System cognitive function
• Endocrine
• Immune function
• Fracture
• Cardiovascular
• Cancer biology
• Misuse and addiction

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Long term harm from opioids?

• No studies of long term outcomes (gt1 year) from
  opioid Rx compared to no opioid
• Increased risk of
• Sexual dysfunction OR 1.45 (CI -1.87)
• Fractures OR 1.27 (CI 1.21-1.33)
• Myocardial infarction OR 1.28 (CI 1.19-1.37)
• Abuse wide range up to 37
• Overdose HR 5.2 (CI 2.1-12.5)
• Motor vehicle accident OR 1.24-1.42

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Opioid endocrinopathy

• Hypothalamic-pituitary-adrenal axis dysfunction
• and/ or
• Hypothalamic-pituitary-gonadal axis
• Symptoms of hypogonadism, adrenal dysfunction
• Coupled with such disorders as osteoporosis and
  mood disturbances

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• Testosterone levels in men secondary
  hypogonadism with reduced pituitary hormones (LH,
  FSH)
• Dose related
• HADs higher
• Fatigue
• Poorer survival (OR of death2.87, plt0.001)

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Mx of hypogonadism necessary?
Discontinue opioid therapy
Switch opioid
Hormone supplementation
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Effect of opioids on wind up

• HV Healthy volunteers
• OA Opioid misuse
• CNCP Chronic non-malignant pain
• CP Cancer pain
• plt0.0001

Implications for Rxing pain?

• Opioid-associated sensory dysfunction

Bathgate et al, EFIC, Sept 2011
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Opioids an the immune system Toll like receptors
Opioids
Intracellular signaling pathways
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Opioids and the immune system central effects

• Opioid activity at TLRs elicit proinflammatory
  reactivity (similar to endotoxin) from glia, the
  immunocompetent cells of the central nervous
  system
• Includes release of cytokines and chemokines and
  associated disruption of glutamate homeostasis
• elevated neuronal excitability
• decreased opioid analgesic efficacy
• heightened pain states

Hutchinson MR. Et al. Pharmacological Reviews.
63(3)772-810, 2011
Wang X. et al, Proc Nat Acad Sci.109(16)6325-30,
2012
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Opioid effects on cytokines
Cong D et al, SPaRC 2014
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Opioids and cancer neurobiology
?
Colvin et al, BJA, August, 2012
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Pain assessment

• Response to opioids
• Tolerance
• ?OIH

Previous experience of healthcare
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Opioid misuse

• Many studies exclude patients with a Hx of
  misuse, definitions vary
• Misuse often not reported event rate of 0.27
  in Cochrane review (Noble, 2010)
• Prediction limited evidence for validated tools
  or urine drug testing

Low risk High risk
Addiction 0.19 3.27
Adverse drug-related behaviour 0.59 11.5
(Fishbain, 2008) (Fishbain, 2008)
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Increasing Prescription Drug Abuse
Drug Abuse Warning Network
National Household Survey On Drug Use and Health
Portenoy, Beth Israel, New York
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Substance misuse pain relievers

• 5.1 million users of pain relievers
• 55 got the pain relievers from a friend or
  relative for free
• 11.4  bought them from a friend or relative (cf
  8.9 from 2007-2008)
• 4.8  took them from a friend or relative without
  asking.

SAMHSA, 2011
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Opioid prescribing in Scotland 2003-2012

• Total of 3.7M in 2003
• Increase to 5.9M total paid items in 2012
• Increase of 63 in 10 years
• In 2012 gt4.8M weak gt1M strong opioid
  prescriptions
• 18 of population had opioid script in 2012

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OPIOIDS AND SCOTTISH INDEX OF MULTIPLE
DEPRIVATION (SIMD)
If in most deprived area 3.5 times more likely to
be prescribed a strong opioid
SIMD quintiles 1 most deprived, 5least deprived
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Opioid related mortality
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Questions?
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Which opioid?

• Methadone
• Buprenorphine
• Subutex
• Suboxone (with naloxone)
• DHC (unlicensed use)
• Avoid short acting if possible

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Assessment history pain and substance misuse

• Pain
• Is there likely to be a neuropathic component?
• Substance misuse history
• Stable/ chaotic prescription? Support?
• IVDA Hep C/ HIV (BBV) status and Rx
• Alcohol stimulants / or benzos cannabis
  NPAs gabapentin
• Mental Health
• Social history/ Child protection issues

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Assessment examination pain and substance
misuse

• Pain
• Sensory changes/ ? neuropathic
• Motor impairment/ impact on function
• Substance misuse history
• Toxicology urine / oral swab
• Track marks
• Intoxication

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Management

• Early assessment explanation
• Non-pharmacological eg TENS (also acupuncture)
• Nerve blocks/ regional techniques

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Management

• Pharmacological
• Non-opioids NSAIDs
• Avoid cyclizine
• ?Gabapentin / Pregabalin
• Strong opioids if needed
• monitoring important
• split dose
• ? buprenorphine

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Opioids and cancer neurobiology

• Up regulation of MORs (non-small cell lung ca)
• Rodent studies - MOR over expression -
  increased tumour growth and metastases
• Peripheral MOR antagonist, methylnaltrexone,
  prevented tumour growth (similar to silencing MOR
  expression )

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Opioids and cancer

• Population based study (n42,000) of patients
  undergoing colectomy ( 22 -epidural analgesia)
  5 year survival better in epidural group cf
  "traditional pain management
• Retrospective study (n655) of colorectal
  cancer increased risk of death up to 5 years
  later in patients receiving patient controlled
  analgesia cf epidural analgesia, only in rectal,
  but not colon cancer.

Cummings KC et al. Anesthesiology 2012
116797-806. Gupta A et al. BJA 2011 107164-170

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Assessment The effect of patient expectation?

• Remifentanil a potent opioid analgesic?
• Constant dose burn - manipulate expectation

Behavioural effects of the contextual modulation
of opioid analgesia
Bingel U et al. Sci Transl Med 2011370ra14-70ra1
4
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Cortical correlates of behaviour
Bingel U et al. Sci Transl Med 2011370ra14-70ra1
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Pain studies design problems?
Overestimation of effect
Little difference from placebo
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Endocrine effects of opioids

• Hypogonadism
• Low LH, oestradiol, testosterone (free and total)
• Symptoms
• Reduced libido, irregular menses
• Low energy
• Depression
• Poor concentration
• Reduced physical performance