PAIN AND ITS MANAGEMENT IN TRIGEMINAL NEURALGIA CANCER

By

Sakhawat Rehman

Department Of Pharmacology and Toxicology

Trigeminal Neuralgia

Trigeminal neuralgia (TN), is a chronic pain condition that affects the trigeminal or 5th cranial nerve, one of the most widely distributed nerves in the head.

 TN is a form of neuropathic pain

2 Types Type 1" or TN1)

Type 2" or TN2),

Trigeminal Nerve

The trigeminal nerve is one of 12 pairs of nerves that are attached to the brain. The nerve has three branches that conduct sensations from the upper, middle, and lower portions of the face, as well as the oral cavity, to the brain. 

ophthalmic, or upper, branch

The maxillary, or middle, branchThe mandibular, or lower, branch

Branches

What causes trigeminal neuralgia?

Blood vessel pressing on the trigeminal nerve.

Sclerosis,

Tumours

Physical Injury

Although there is general agreement that none of the many existing theories fully explain all known characteristics of TGN pain

More specifically, the existing evidence suggests that a slowly evolving process, whether a compression exerted on the nerve by a blood vessel or tumour or alteration of neural functions by an plaque at the level of the dorsal root entry zone, leads to increased excitability in some of the trigeminal afferents and subsequently to typical TGN.

symptoms of trigeminal neuralgiaPain varies, depending on the type of

TN, and may range from sudden, severe, and stabbing to a more constant, aching, burning sensation. 

The intense flashes of pain can be triggered by vibration or contact with the cheek

The pain may affect a small area of the face or may spread. 

How is TN diagnosed?

Special MRI imaging

Clinical Signs

Differential diagnosis of TGN. *SUNCT, Short‐lasting, unilateral, neuralgiform headcahe with conjunctival injection and tearing; **CPH, chronic paroxysmal hemicrania.

Condition Location of pain Duration of pain or attack

Shooting pain or paroxysms

Autonomic symptoms

Pain relief with carbamazepine Comments

Cluster headacheRetrobulbar, cheek, chin 20 min to hours

Only superimposed on deep dull pain Prominent Slight

Triptans help Alcohol provokes

SUNCT* Forehead, retrobulbar 5 s to several minutes Yes Prominent NoneAlmost exclusively inwomen; rare

CPH** Forehead, retrobulbar 2–45 min No Prominent NoneResponsive to indomethacin

Cracked tooth syndrome Upper jaw lower jaw Seconds Yes None None

Provoked on biting and chewing

Jabs and jolts syndrome Anywhere in the head Seconds Yes None Good

No precipitating factors

Post‐herpetic neuralgia

Forehead, eye, cheek (rarely) Continuous

Superimposed background pain Variable, mild

Variable, usually modes

History of shingles Tactile allodynia,Sensory impairment

Giant cell arteritisForehead, neck, temple Continuous None None None Jaw claudication

FeatureTrigeminal Neuralgia

Atypical Facial Pain

Prevalence Rare Common

Main location Trigeminal area Face, neck, ear

Pain duration Seconds to 2 minutes Hours to days

Character Electric jerks, stabbing Throbbing, dull

Pain intensity Severe Mild to moderate

Provoking factors Light touch, washing, shaving, eating, talking

Stress, cold

Associated symptoms None Sensory abnormalities

Distinguishing Features Between Trigeminal Neuralgia and Atypical Facial Pain

Treatment

Treatment options include medicines, surgery, and complementary approaches.

Drug Initial dose Maintenance dose

Carbamazepine 200 mg/ day 400–1200 mg /day

Oxcarbazepine 300 mg /day 600–1200 mg /day

Phenytoin 300 mg 200–400 mg

Lamotrigine 25–50 mg 200–400 mg

Baclofen 10 mg 30–80 mg

Surgery

Rhizotomy

Neurectomy

Complementary approaches

Some individuals manage trigeminal neuralgia using complementary techniques, usually in combination with drug treatment. 

Yogacreative visualizationaroma therapy Acupuncturevitamin therapynutritional therapy.

We can’t rely purely on complementary medicine but it requires combination…

Cancer

Cancer also known as a malignant tumor or malignant neoplasm, is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body.

Benign Tumour

Malignant Tumour

Pain in cancer

Pain

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.

Acute

chronic

Nociceptive Neuropathic

Causes of Pain in Cancer

Tumor-related

Tumors cause pain by crushing or infiltrating tissue, triggering infection or inflammation, or releasing chemicals that make normally non-painful stimuli painful..

Treatment-related

Potentially painful cancer treatments include

Immunotherapy which may produce joint or muscle pain;

Radiotherapy, which can cause skin reactions, enteritis, fibrosis, myelopathy, bone necrosis, neuropathy.

Chemotherapy, often associated with mucositis, joint pain, muscle pain, peripheral neuropathy.

Infection

PathophysiologyCancer pain shares the same neurophysiologic pathway as non-cancer pain. This process of nociception involves activation of the sensory afferents by persistent noxious stimuli, transduction, transmission, modulation, and perception.

1. Assess and re-assess the pain

  • Causes, onset, type, site, duration, intensity, relief and temporal patterns of the pain  • Presence of the trigger factors and the signs and symptoms associated with the pain  • Use of analgesics and their efficacy and tolerability

2. Assess and re-assess the patient

  • The clinical situation by means of a complete/specific physical examination and the specific radiological and/or biochemical investigations  • The presence of interference of pain with the patient's daily activities, work, social life, sleep patterns, appetite, sexual functioning and mood  • The impact of the disease and the therapy on the physical, psychological and social conditions  • The presence of a caregiver, the psychological status, the degree of awareness of the disease, anxiety and depression and suicidal ideation, his/her social environment, quality of life, spiritual concerns/needs  • The presence and intensity of signs, physical and/or emotional symptoms associated with cancer pain syndromes  • The functional status  • The presence of opiophobia

3. Assess and re-assess your ability to inform and to communicate with the patient and the family

  • Take time to spend with the patient and the family to understand their needs

Guidelines for a correct assessment of the patient with pain

Validated and most frequently used pain assessment tools.

Ripamonti C I et al. Ann Oncol 2011;22:vi69-vi77

ManagementPsychological Coping strategies

Psychosocial interventions

Medications

WHO's cancer pain ladder for Pain Management

Management of cancer pain:

WHO: Step 1…Substance

Widely available forms and strengths

Time to onset (min) Caution Maximal daily dose

Acetaminophen (paracetamol)

Tablets, suppositories 500–1000 mg

15–30 Hepatotoxicity 4 × 1000 mg

Acetylsalycic acid Tablets 500–1000 mg 15–30GI toxicity, allergy, platelet inhibition

3 × 1000 mg

IbuprofenTablets 200–400–600 mg; tablets 800 mg modified release; topical gels

15–30; 120+ GI and renal toxicity4 × 600 mg; 3× 800 mg modified release

KetoprofenTablets 25–75 mg; tablets 100–150–200 mg modified release

30+ GI and renal toxicity 4 × 75 mg; 2 × 200 mg

DiclofenacTablets 25–50–75 mg; tablets 100 mg modified release

30–120 GI and renal toxicity 4 × 50 mg; 2 × 100 mg

Mefenamic acid Capsules 250–500 mg 30+ GI and renal toxicity 4 × 500 mg

Naproxen Tablets 250–375–500 mg 30+ GI and renal toxicity 2 × 500 mg

SubstanceWidely available forms and strengths

Relative effectiveness compared with oral morphine

Duration of effectiveness (h)

Maximal daily doseStarting dose without pretreatment

DihydrocodeineModified-release tablets 60–90–120 mg

0.17 12 240 mg 60–120 mg

Codeine Tablet 15–30–60 mg 4–6 360 mg 15–60 mg

Tramadol

Drops 100 mg/ml; capsules 50 mg

0.1–0.2 2–4 400 mg 50–100 mg

Modified-release tablets 100–150–200 mg

0.1–0.2 12 400 mg 50–100 mg

Comparison of selected opioids for mild to moderate pain (WHO step II)

Comparison of selected opioids for moderate to severe pain (WHO step III)

Substance RouteRelative effectiveness compared with oral morphinea

Maximal daily doseStarting dose without pretreatment

Morphine sulfate Oral 1 No upper limitb 20–40 mg

Morphine i.v. 3 No upper limitb 5–10 mg

Oxycodone Oral 1.5–2 No upper limitb 20 mg

Hydromorphone Oral 7.5 No upper limitb 8 mg

Fentanyl transdermal TTS + 4c No upper limitb 12 μg/hd

Buprenorphine Oral 75 4 mg 0.4 mg

Buprenorphine i.v. 100 3 mg 0.3–0.6 mg

Buprenorphine transdermal TTS + 4c 140 μg/h 17.5–35μg/h

Methadone Oral 4–8–12e No upper limitb 10 mg

Nicomorphine Oral 1 20 mg 5 mg

Nicomorphine i.v. 3 20 mg 5 mg

Selected adjuvant drugs for neuropathic pain

SubstanceWidely available forms and strengths (mg)

Activity SedationRange of daily doses (mg)

Amitryptiline Tablets 25–50 Antidepressive +++ 50–200

Clomipramine Tablets 10–75 Antidepressive (+) 50–200

Nortriptyline Tablets 10–25 Antidepressive + 50–225

Fluoxetine Tablets 20 Antidepressive + 20–80

Duloxetine Tablets 30–60 Antidepressive + 60–120

Carbamazepine Tablets 200–400 Antiepileptic + 400–1600

Gabapentin Tablets 200–300–400–800 Antiepileptic ++ 900–3600

PregabalinTablets 25–50–75–100–150–200–300 mg

Antiepileptic + 150–600

Haloperidol Drops, tablets, vials Neuroleptic + 3–20

ChlorpromazineDrops, tablets, suppositories, vials

Neuroleptic + 25–200

Usually the lowest doses of antidepressants and neuroleptics are sufficient as an adjunct to opioids unless severe depression or major psychosis has to be treated with higher doses as appropriate.

Radiation Radiotherapy is used when drug treatment is failing to control the pain of a growing tumor, such as in bone metastisis

Radiopharmaceuticals that target specific tumors have been used to treat the pain of metastatic illnesses. Relief may occur within a week of treatment and may last from two to four months.

Neurolytic block

Cutting or destruction of nervous tissue

Patient-controlled analgesia

Intrathecal pumpAn intrathecal pump infuses an opioid such as morphine directly into the fluid-filled space (the subarachnoid cavity) between the spinal cord and its protective sheath, providing enhanced analgesia with reduced systemic side effects.

Long-term epidural catheterThe outer layer of the sheath surrounding the spinal cord is called the dura mater. Between this and the surrounding vertebrae is the epidural space, filled with connective tissue, fat and blood vessels, and crossed by the spinal nerve roots. A long-term epidural catheter may be inserted into this space for three to six months, to deliver anesthetics or analgesics. The line carrying the drug may be threaded under the skin to emerge at the front of the patient, a process called "tunneling", recommended with long-term use to reduce the chance of any infection at the exit site reaching the epidural space.

Spinal cord stimulation

Deep brain stimulation

References:Hackley, CE (1869). A text-book of practical medicine. D. Appleton & Co. p. 292. Retrieved 2011-08-01.

Bayer DB, Stenger TG (1979). "Trigeminal neuralgia: an overview". Oral Surg Oral Med Oral Pathol 48 (5): 393–9. doi:10.1016/0030-4220(79)90064-1•"Science Links Japan | Trigeminal Neuralgia-A View of Opioid Treatment". Sciencelinks.jp. 2009-03-18. Retrieved 2013-10-09.

Sindrup, SH; Jensen, TS (2002). "Pharmacotherapy of trigeminal neuralgia". Clin J Pain 18 (1): 22–7. doi:10.1097/00002508-200201000-00004

"Cancer Fact sheet N°297". World Health Organization. February 2014. Retrieved 10 June 2014.

Hanahan, Douglas; Weinberg, Robert A. (2011). "Hallmarks of Cancer: The Next Generation". Cell 144 (5): 646–74

Little JB (2000). "Chapter 14: Ionizing Radiation". In Kufe DW, Pollock RE, Weichselbaum RR, Bast RC Jr, Gansler TS, Holland JF, Frei E III. Cancer medicine (6th ed.). Hamilton, Ont: B.C. Decker. ISBN 1-55009-113-1.

Mantovani A (June 2010). "Molecular pathways linking inflammation and cancer". Current Molecular Medicine (review) 10 (4): 369–73.

Croce CM (January 2008). "Oncogenes and cancer". N. Engl. J. Med. 358 (5): 502–11. doi:10.1056/NEJMra072367