This document discusses chronic pain management and treatment options. It notes that chronic pain is influenced by many physical and psychological factors, requiring multimodal interventions. Common drug classes used include antidepressants, anticonvulsants, opioids, and local anesthetics. Antidepressants are effective for neuropathic pain and may enhance inhibitory pathways and act on other receptors. Anticonvulsants are commonly used for neuropathic pain by reducing neuronal excitability. Opioids can be effective but have side effects like nausea and constipation. Non-pharmacological therapies and more advanced interventions are also discussed.

1. Chronic pain management
By Atalay Eshetie Demilie

2. Introduction
• Complex and many factors influence pain experience.
• Therefore, need multimodal interventions.
• Both physical and psychological, delivered in parallel.
• Pharmacotherapy plays an important role.
• Often refractory to conventional analgesic therapy.
• Non-analgesic drugs are frequently used.
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3. Common classes of drugs chronic pain clinic
• Anti-depressants
• Anti-epileptics
• Opioids
• Local anesthetics and anti- arrhythmics
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4. Anti-depressant drugs
• Almost 50% of patients with pain have depression.
• Use lower doses than used for treating depression.
• More effective in the absence of depression.
• Unknown mechanism.
• Likely inhibition of re-uptake of neurotransmitters in the CNS.
• Therefore; enhance descending inhibitory pathways.
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5. • Additionally, act on other receptors.
E.g. alpha adrenergic, histaminergic and NMDA
Sodium and calcium channels blockade
Weak stimulatory action in µ-opioid receptors
• Most commonly used are the first generation tricyclic antidepressants
including amitriptyline, doxepin, clomipramine and dosulepin.
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6. Side-effects (commonly limit their use) include
• Sedation and anticholinergic effects,
• Particularly dry mouth.
• Constipation and urinary retention are well documented.
• The drugs have a number of effects on the heart including
slowing of atrioventricular and intraventricular conduction.
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7. • Mixed reuptake inhibitors such as amitriptyline are
more effective than selective agents.
• Emphasizing the importance of both serotonergic
and noradrenergic pathways in pain perception.
• Relieve other common symptoms in patients with
chronic pain, such as sleep disorder.
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8. • Although anti-depressants have been used for over thirty years
to manage neuropathic pain, in the UK no antidepressant has a
product license for this indication.
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9. Clinical and practical issues in using ADs
• Still one of first line drugs.
• In multiple large scale RCTs, antidepressants were found
beneficial. Mostly in patients with post-herpetic neuralgia,
painful diabetic neuropathy and central pain.
• Satisfactory NNT.
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10. • Once daily. Night dose. >>> help in sleep disturbance.
• Morning sedation.
• If day time somnolence persist >>> take earlier.
• Titrate to efficacy and side effects
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11. Commonly used doses of antidepressants for chronic pain
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12. Anti-epileptic drugs
• Widely used in pain clinics to treat neuropathic pain.
• First phenytoin, then carbamazepine.
• Good for post-herpetic neuralgia, trigeminal neuralgia, painful
diabetic neuropathy, and post-stroke pain.
• Not robust for phantom limb pain and spinal cord injury.
• Multiple mechanisms of action.
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13. • Older anti-epileptics reduce neuronal excitability by
frequency-dependent blockade of Na+ channels.
• Carbamazepine remains the treatment of choice in
trigeminal neuralgia.
• About 70% of patients get significant pain relief.
• Oxcarbazepin with less side effects.
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14. • Lamotrigine acts at sodium channels and suppresses
release of glutamate.
• Sodium valproate elevates levels of GABA.
• Gabapentin and pregabeline have inhibitory action
in voltage-gated calcium channels.
• With gabapentin, at least 50% pain reduction.
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15. Side effects of AEs:
• Acute toxicity.
• CNS, gastrointestinal and hematological systems
are commonly affected.
• Usually do not lead to discontinuation.
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17. Opioids
• Strong opioids may be effective when other therapies fail.
• Preferably slow release preparations are used at a low dose
• Titrated against side effects and pain.
• Oxycodone, tramadol, fentanyl and morphine found effective.
• No robust evidence on superiority.
• Limitations?
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18. • Common opioid-related adverse effects include:
Nausea and vomiting, constipation, sedation,
dizziness and respiratory depression.
• These effects generally decrease after long-term
treatment, except constipation.
• Long-term administration may be associated with
immunological changes, hypogonadism, hyperalgesia
and risk of addiction.
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19. • Tramadol has properties of serotonin and
norepinephrine agonists.
• There is an increased risk of seizures in patients with
previous epilepsy or receiving drugs reducing the
seizure threshold such as TCAs.
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20. Local anesthetics and anti-arrhythmics
• Suppress hyper-excitability by sodium channel blockade.
• Low-dose lidocaine may block glutamate-evoked activity
in the dorsal horn of the spinal cord.
• Primarily used to treat postoperative pain and more
recently for deafferentation pain, central pain and
diabetic neuropathy.
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21. • The drug is not suitable for long-term use as it cannot
be given orally but continues to be used IV.
• Lidocaine 5% is available as a 10 X 14 cm patch.
• Shown to have efficacy and tolerability in the
management of post-herpetic neuralgia.
• Mexiletine is the oral analogue of lidocaine with
disappointing efficacy with bad side effect profile.
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22. • Gastrointestinal side-effects of Mexiletine are very
common and frequently limit treatment.
• Other problems include worsening of existing arrhythmias
and neurological symptoms (particularly tremor).
• The use of other antiarrhythmic agents is now precluded
because of the incidence of severe adverse events.
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23. Other pharmacological interventions
• Ketamine is an NMDA antagonist.
• Successfully used in sub-anesthetic doses for neuropathic pain.
• The side effects include psychomimetic effects: limit its usefulness.
• Generally used in limited response to standard treatments and
display features of central wind up phenomenon.
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24. • Methadone is believed to have some action
at the NMDA receptor.
• It may well have a place in the management
of chronic pain.
• It is not easy to titrate but has advantage of a
long duration of action.
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25. Non-pharmacologic therapies
• Simple measures such as massage, exercise and
physiotherapy can help in producing marked
functional improvements.
• Hypnosis, meditation, TENS and acupuncture.
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26. Advanced interventions
• Neural blockade or ablation
• Spinal cord stimulations
• Surgical and chemical sympathectomy Surgery.
• e.g. Microvascular decompression for some
types of trigeminal neuralgia
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27. Chronic post-surgical pain (CPSP)
• Multiple perioperative risks.
• Age was found inversely related with CPSP.
• Genetic susceptibility has central role.
• Malignancies
• Infections
• Pre-existing pain
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28. Incidence of CPSP
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29. Preventive techniques
• Pre-emptive regional analgesia.
• Paravertebral block initiated before incision and
continued into the postoperative period in
thoracic and breast cancer.
• Epidural analgesia reduces the incidence of CPSP
in patients undergoing thoracotomy and
laparotomy.
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30. • Perioperative IV ketamine infusion has been
used to prevent development of CPSP in
patients undergoing mastectomy,
thoracotomy, and rectal cancer surgery.
• Clonidine added in LA may reduce CPSP.
But limited data.
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31. • Some patients develop neuropathic pain symptoms in
the immediate postoperative period.
• Anti-neuropathic medications such as gabapentin are
increasingly being used by the acute pain service.
• It is not known whether treating neuropathic pain in
the postoperative setting reduces the development of
chronic neuropathic pain after surgery.
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32. Thank You!
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