Pain pathways & Pain management for Pharm.D

Pharmacotherapeutics-3, classification, pain pathways, clinical presentation and clinical management of pain.

1. PAIN MANAGEMENT T.SOUJANYA PHARM.D

2. CONTENTS: Definition Epidemiology Classification of pain Pathophysiology/pain pathways Clinical presentation of pain Pain management WHO analgesic ladder Reference/bibliography

3. DEFINITION: The word pain is derived from Latin word “peone” and the Greek word “poine” meaning “penalty or punishment”. According to “International Association for the Study of Pain”, the pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage or in terms of such damage.

4. EPIDEMIOLOGY: Pain is the most common symptoms that provokes people to seek medical attention. Despite this, the epidemiology of pain is not as well documented as it is the incidence of many chronic diseases. 50 million Americans are partially or totally disabled because of pain. The annual cost of pain to American society can be estimated to be in the million dollars. In the Michigan pain study, 70% of chronic pain patients claimed to have pain despite treatment, with 22% believing that treatment worsened pain.

5. CLASSIFICATION OF PAIN: Pain Acute pain Chronic pain Somatic pain Visceral pain Nociceptive pain Neuropathic pain

6. 1. ACUTE PAIN: Acute pain is defined as the pain of a shorter duration that subsides as the healing process occurs. This pain may range from mild to severity in intensity. Causes of acute pain include: Post operative pain Procedural pain Traumatic pain

7. CONTD… a) SOMATIC PAIN: It result of activation of nociceptors (sensory receptors) sensitive to noxious stimuli in cutaneous or deep tissues. It is experienced locally and described as constant, aching and gnawing. It is the most common type in cancer patients. b) VISCERAL PAIN: It is mediated by nociceptors. It is described as deep, aching and colicky. It is poorly localized and often referred to cutaneous sites, which may be tender. In cancer patients, results from stretching of viscera by tumour growth.

8. 2. CHRONIC PAIN: It usually lasts longer than 3-6 months and ranges in intensity from mild to severe. Chronic pain associated with malignancy includes: The pain of cancer Acquired immuno deficiency syndrome (AIDS) Multiple sclerosis Sickle cell anaemia End stage organ system failure

9. CONTD… a) NOCICEPTIVE PAIN: It may be visceral or somatic. It is usually derived from the stimulation of pain receptors. It may arise from tissue inflammation, mechanical deformation, ongoing injury or destruction. It responds well to common analgesic medications and non drug strategies. b) NEUROPATHIC PAIN: It involves the central and peripheral nervous system. It does not respond as predictably as nociceptive pain to conventional analgesics. It may respond to adjuvant analgesic drugs.

10. PATHOPHYSIOLOGY: The pathophysiology of pain is mainly classified into two pathways: Nociceptive pathway Neuropathic pathway

11. 1. NOCICEPTIVE PATHWAY: Nociceptive pain typically is classified either: Somatic: arising from skin, bone, joint, muscle or connective tissue Visceral: arising from internal organs such as large intestine/pancreas The mechanisms involved in nociceptive pathway are: Stimulation Transmission Perception Modulation

12. CONTD… a) STIMULATION: The first step leading to sensation of pain is the stimulation of free nerve endings known as nociceptors. These receptors are found in both somatic and visceral structures and are activated & sensitized by mechanical, thermal & chemical impulses. Noxious stimulus sensitizes and/or stimulates nociceptors and causes the release of neurochemicals like bradykinins, K + , prostaglandins, histamine, leukotrienes, serotonin and substance P that also sensitize and/or stimulate nociceptors. This activation leads to the production of action potential (AP).

13. CONTD… b) TRANSMISSION: The action potential continues from the site of noxious stimulus to the dorsal horn of spinal cord and then ascends to higher centres in the CNS. Transmission takes place in at least 5 pathways: Spinothalamic tract Spinoreticular tract Spinomesencephalic tract Dorsal column post synaptic spinomedullary pathway Propriospinal multisynaptic ascending systems

14. CONTD… c) PERCEPTION: Conscious experience of pain d) MODULATION: Inhibition of nociceptive impulses. Neurons from the brain stem descend to the spinal cord and release substances such as endogenous opioids, serotonin and norepinephrine that inhibit transmission of nociceptive impulses.

15. Noxious (painful) stimuli 1) stimulation Activation of peripheral nervous system Production of action potential (AP) 2) Transmission AP reaches dorsal horn of spinal cord Activation of CNS at spinal cord 4) Modulation Transmission of pain signals to brain Nociception inhibiting neurons Brain responds to stimuli (pain) 3) perception

16. 2. NEUROPATHIC PATHWAY: Neuropathic pain is distinctly differ from nociceptive pain. It is the pain sustained by abnormal processing of sensory input by the central or peripheral nervous system. e.g. low back pain, diabetic neuropathy, post herpetic neuralgia, cancer related pain, spinal cord injury, multiple sclerosis etc. The mechanism responsible may be the nervous system’s endogenous dynamic nature. Nerve damage or persistent nerve stimulation may cause pain circuits to rewire themselves both anatomically and biochemically. This produces:

17. CONTD… Spontaneous nerve stimulation Autonomic neuronal pain stimulation Progressive increase in the discharge of dorsal horn neurons Clinically, patients present with spontaneous pain transmission, exaggerated painful response to normally noxious stimuli (hyperalgesia) or painful response to normally non noxious stimuli (allodynia).

18. Nerve damage/ persistent stimulation Results in Rewiring of pain circuits both anatomically and biochemically causing finally lead to Neuropathic pain Spontaneous nerve stimulation Autonomic neuronal stimulation Increased discharge of dorsal horn neurons

19. CLINICAL PRESENTATION OF PAIN: 1. GENERAL: Patients may be in obvious acute distress (trauma pain) or appear to have no noticeable suffering (chronic/persistent). 2. SYMPTOMS: Pain can be described as sharp, dull, burning, shock like, tingling, shooting, radiating, fluctuating in intensity and varying in location. Overtime, the same pain stimulus may cause symptoms that completely change ( e.g. sharp to dull, obvious to vagus). Non specific symptoms include anxiety, depression, fatigue, insomnia, anger and fear.

20. CONTD… 3. SIGNS: Acute pain can cause hypertension, tachycardia, diaphoresis, mydriasis and pallor, but these signs are not diagnostic. In some acute cases and in most chronic/persistent pain, there may be no obvious signs. 4. LABORATORY TESTS: Pain is always subjective There are no laboratory tests that can diagnose pain Thus pain is best diagnosed based on patient description and history.

21. PAIN MANAGEMENT: GOALS OF TREATMENT: To decrease intensity and duration of pain To decrease suffering and disability associated with pain Minimize ADRs or intolerance to pain management therapy Monitor and evaluate for therapeutic and unwanted effects Improve patient’s quality of life

22. NON-PHARMACOLOGICAL TREATMENT: Radiotherapy: For the management of bone metastasis. Physiotherapy: Spinal manipulation, massage, application of heat or cold. Stimulation therapy: Transcutaneous electrical nerve stimulation (TENS). Physiological intervention: Cognitive, behavioural and social therapy.

23. PHARMACOLOGICAL TREATMENT: 1. NON-OPIOID ANALGESICS: MOA: These drugs except acetaminophen prevent formation of prostaglandins, produced in response to noxious stimuli, thereby decrease the number of pain impulses received by the CNS. Non-opioid analgesics/NSAIDs Prevent prostaglandin synthesis Decrease no. of pain impulses Relieve pain

24. CONTD… ADRs: GI effects include nausea, vomiting, diarrhea/constipation, dyspepsia, epigastric pain, bleeding ulceration, hypersensitivity reactions. Dose: Aspirin: 150-600mg orally BD Acetaminophen: 325-650mg orally Meclofenamate: 50-100mg orally Mefenamic acid: 250-500mg orally Etodolac: 400mg or 200-400mg orally Diclofenac: 50-100mg IM or orally

25. CONTD… 2. OPIOID ANALGESICS: MOA: Opioids produce their actions by interacting with various opioid receptors ( µ , δ , κ ) that are located in spinal, supra spinal and peripheral nerves. Opioid analgesics binds Opioids receptors Activation of opioid receptors Close voltage sensitive Ca +2 channels & stimulate K + efflux Decreases transmission of nociceptive impulses

26. CONTD… ADRs: Nausea, vomiting, constipation, respiratory depression, hypotension due to vasodilation, drowsiness, confusion, itching, skin rashes etc. Dose: Morphine: 10-50mg orally or 10-15mg IM or SC Codeine: 30-60mg orally Methadone: 2.5-10mg oral/IM Tramadol: 50-100mg oral/IM

27. 3. ADJUVANT DRUGS: Tricyclic antidepressants: Amitriptyline Anti convulsants: Carbamazepine, sodium valproate Corticosteroids: Prednisolone, dexamethasone Anxiolytics: Diazepam, lorazepam Muscle relaxants: Baclofen

28. WHO ANALGESIC LADDER:

29. REFERENCE/BIBLIOGRAPHY: Textbook of Pharmacotherapy: A Pathophysiologic approach by Joseph T. Dipiro.