💊Intro to Pharmacology Unit 6 – Pain Management & Anesthetics in Pharmacology

Key Concepts and Definitions

• Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage
• Nociception refers to the neural processes of encoding and processing noxious stimuli
• Acute pain is sudden, short-lived pain that serves as a warning signal of tissue damage or a threat to the body
• Chronic pain persists beyond the normal healing time and lacks the acute warning function of physiological nociception
• Allodynia is pain due to a stimulus that does not normally provoke pain (e.g., light touch)
• Hyperalgesia is an increased response to a stimulus that is normally painful
• Central sensitization involves increased responsiveness of nociceptive neurons in the central nervous system to their normal or subthreshold afferent input

Pain Physiology and Pathways

• Nociceptors are specialized sensory neurons that detect noxious stimuli and transduce them into electrical signals
  • Nociceptors respond to mechanical, thermal, and chemical stimuli
• Afferent nerve fibers transmit pain signals from the periphery to the spinal cord and brain
  • A-delta fibers are myelinated and conduct fast, sharp, localized pain
  • C fibers are unmyelinated and conduct slow, dull, diffuse pain
• The spinothalamic tract is a major ascending pathway that carries pain signals from the spinal cord to the thalamus
• The thalamus relays pain signals to various cortical areas involved in pain perception (e.g., somatosensory cortex, anterior cingulate cortex)
• Descending modulatory pathways from the brain can inhibit or facilitate pain transmission at the spinal level
  • The periaqueductal gray (PAG) and rostral ventromedial medulla (RVM) are key regions involved in descending pain modulation

Types of Pain and Assessment

• Nociceptive pain results from actual or threatened damage to non-neural tissue and is due to the activation of nociceptors
  • Somatic pain originates from skin, muscles, joints, or bones (e.g., arthritis pain)
  • Visceral pain originates from internal organs (e.g., appendicitis pain)
• Neuropathic pain is caused by a lesion or disease of the somatosensory nervous system
  • Examples include diabetic neuropathy, postherpetic neuralgia, and central post-stroke pain
• Mixed pain has both nociceptive and neuropathic components (e.g., cancer pain)
• Pain assessment tools include numeric rating scales, visual analog scales, and the McGill Pain Questionnaire
• Multidimensional pain assessment considers pain intensity, quality, location, duration, and impact on daily activities

Pharmacological Approaches to Pain Management

• The World Health Organization (WHO) analgesic ladder provides a stepwise approach to pain management
  • Step 1: Non-opioids (e.g., acetaminophen, NSAIDs) for mild pain
  • Step 2: Weak opioids (e.g., codeine, tramadol) for moderate pain
  • Step 3: Strong opioids (e.g., morphine, fentanyl) for severe pain
• Multimodal analgesia combines different classes of analgesics with complementary mechanisms of action
• Adjuvant medications (e.g., antidepressants, anticonvulsants) can be used to treat neuropathic pain or enhance the efficacy of primary analgesics
• Patient-controlled analgesia (PCA) allows patients to self-administer pre-programmed doses of analgesics, typically opioids
• Topical analgesics (e.g., lidocaine patches, capsaicin creams) can provide localized pain relief with minimal systemic side effects

Major Classes of Analgesics

• Non-steroidal anti-inflammatory drugs (NSAIDs) reduce pain and inflammation by inhibiting cyclooxygenase (COX) enzymes
  • Examples include ibuprofen, naproxen, and celecoxib
• Acetaminophen (paracetamol) has analgesic and antipyretic effects but lacks significant anti-inflammatory properties
  • Its mechanism of action is not fully understood but may involve inhibition of central prostaglandin synthesis
• Opioids act on opioid receptors (mu, kappa, delta) to produce analgesia, sedation, and respiratory depression
  • Examples include morphine, oxycodone, and fentanyl
• Antidepressants, particularly tricyclic antidepressants (TCAs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), can be effective for neuropathic pain
• Anticonvulsants, such as gabapentin and pregabalin, are used to treat neuropathic pain by modulating calcium channels and reducing neuronal excitability

Anesthetics: Local and General

• Local anesthetics block sodium channels and prevent nerve impulse conduction, causing temporary loss of sensation in a specific area
  • Examples include lidocaine, bupivacaine, and ropivacaine
  • Local anesthetics can be administered via infiltration, nerve blocks, or epidural/spinal routes
• General anesthetics produce a reversible loss of consciousness, analgesia, amnesia, and muscle relaxation
  • Intravenous anesthetics (e.g., propofol, ketamine) are used for induction and maintenance of anesthesia
  • Inhalational anesthetics (e.g., sevoflurane, desflurane) are administered via the respiratory system
• Balanced anesthesia combines different classes of drugs (e.g., intravenous anesthetics, opioids, neuromuscular blockers) to achieve the desired anesthetic effects while minimizing side effects

Drug Interactions and Side Effects

• NSAIDs can interact with anticoagulants, increasing the risk of bleeding
  • NSAIDs may also interact with antihypertensives, reducing their effectiveness
• Opioids can potentiate the sedative effects of benzodiazepines and other central nervous system depressants
  • Combining opioids with monoamine oxidase inhibitors (MAOIs) can lead to serotonin syndrome
• Common side effects of opioids include nausea, vomiting, constipation, sedation, and respiratory depression
  • Long-term opioid use can lead to tolerance, physical dependence, and addiction
• Local anesthetics may cause allergic reactions, cardiovascular toxicity (e.g., hypotension, arrhythmias), and central nervous system toxicity (e.g., seizures) if administered in excessive doses or inadvertently injected into the bloodstream
• General anesthetics can cause hypotension, bradycardia, and postoperative nausea and vomiting (PONV)
  • Malignant hyperthermia is a rare but life-threatening complication of some inhalational anesthetics and succinylcholine

Non-Pharmacological Pain Management Strategies

• Physical therapy and exercise can improve function, reduce pain, and prevent disability
  • Techniques include stretching, strengthening, and aerobic conditioning
• Cognitive-behavioral therapy (CBT) helps patients develop coping skills, modify maladaptive thoughts and behaviors, and improve self-efficacy
• Biofeedback teaches patients to control physiological responses (e.g., muscle tension, heart rate) to reduce pain and stress
• Acupuncture involves the insertion of fine needles at specific points to alleviate pain and promote healing
  • The mechanism of action may involve the release of endogenous opioids and modulation of neurotransmitters
• Transcutaneous electrical nerve stimulation (TENS) delivers low-voltage electrical currents through the skin to reduce pain
  • TENS is thought to work by activating descending inhibitory pathways and releasing endorphins
• Massage therapy manipulates soft tissues to reduce muscle tension, improve circulation, and promote relaxation
• Heat and cold therapy can be used to reduce pain, inflammation, and muscle spasms
  • Heat increases blood flow and relaxes muscles, while cold reduces swelling and numbs the affected area