Pain Management

Definitions and Physiology

Definitions

• Nociception Nociception Sensing of noxious mechanical, thermal or chemical stimuli by nociceptors. It is the sensory component of visceral and tissue pain (nociceptive pain). Pain: Types and Pathways: process through which peripheral receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors transmit information about current (or potential) tissue damage centrally as pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
• Nociceptor Nociceptor Peripheral afferent neurons which are sensitive to injuries or pain, usually caused by extreme thermal exposures, mechanical forces, or other noxious stimuli. Their cell bodies reside in the dorsal root ganglia. Their peripheral terminals (nerve endings) innervate target tissues and transduce noxious stimuli via axons to the central nervous system. Pain: Types and Pathways: receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors in end-organ that detects biochemical changes associated with current or potential tissue damage
• Nociceptive pain Nociceptive pain Dull or sharp aching pain caused by stimulated nociceptors due to tissue injury, inflammation or diseases. It can be divided into somatic or tissue pain and visceral pain. Pain: Types and Pathways: pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways caused by actual or threatened damage to non-neural tissue
• Neuropathic pain Neuropathic pain Caused by lesion or disease affecting the nervous system (PNS or CNS). Pain: Types and Pathways: pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways caused by pathology in the somatosensory nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification
• Peripheral sensitization: pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways perceived at a lower threshold Threshold Minimum voltage necessary to generate an action potential (an all-or-none response) Skeletal Muscle Contraction of peripheral nociceptive stimulation and/or an increase in pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways perception Perception The process by which the nature and meaning of sensory stimuli are recognized and interpreted. Psychiatric Assessment at a given level of peripheral nociceptive stimulation
• Central sensitization Central sensitization Increased responsiveness of nociceptive neurons in the central nervous system to normal or subthreshold input. Pain: Types and Pathways: increased responsiveness of nociceptive neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology in the central nervous system Central nervous system The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. Nervous System: Anatomy, Structure, and Classification to normal or subthreshold input
  • Allodynia: pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways due to a stimulus that does not typically provoke pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Hyperalgesia Hyperalgesia An increased sensation of pain or discomfort produced by minimally noxious stimuli due to damage to soft tissue containing nociceptors or injury to a peripheral nerve. Pain: Types and Pathways/hyperpathia: heightened response to a typically painful stimuli

Physiology

• Complex bidirectional process with phases:
  • Transduction Transduction The transfer of bacterial DNA by phages from an infected bacterium to another bacterium. This also refers to the transfer of genes into eukaryotic cells by viruses. This naturally occurring process is routinely employed as a gene transfer technique. Bacteriology
  • Transmission
  • Modulation
  • Central perception Perception The process by which the nature and meaning of sensory stimuli are recognized and interpreted. Psychiatric Assessment
• Peripheral nerves Peripheral Nerves The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. Nervous System: Histology, both motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology and sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology, are grouped by size and myelination. 
• Pain is experienced in 2 phases:
  1. 1st phase is mediated by the fast-conducting A-delta fibers, associated with an initial sharp pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways (fast pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways).
  2. 2nd phase is mediated by C fibers, associated with a more prolonged and a less intense feeling of pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways (slow, sustained pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways).
• Type-A fibers: large and myelinated Myelinated Internuclear Ophthalmoplegia, thus fast conducting
  • A alpha:
    • Primary receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors of the muscle spindle and Golgi tendon organ
  • A beta:
    • Largest-diameter afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology axon
    • Secondary receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors of the muscle spindle, contribute to cutaneous mechanoreceptors
    • Perceive light touch Light touch Neurological Examination and/or moving stimuli
  • A delta:
    • Free nerve endings that conduct stimuli related to pressure and temperature
    • Action potential Action Potential Abrupt changes in the membrane potential that sweep along the cell membrane of excitable cells in response to excitation stimuli. Membrane Potential conducts at a rate of approximately 20 m/s towards the central nervous system Central nervous system The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. Nervous System: Anatomy, Structure, and Classification (CNS)
  • A gamma:
    • Motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology that control the intrinsic activation of the muscle spindle
    • Do not transmit signals that contribute to pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways under normal conditions (but may in the pathologic state of central sensitization Central sensitization Increased responsiveness of nociceptive neurons in the central nervous system to normal or subthreshold input. Pain: Types and Pathways)
• Type-B fibers:
  • Middle-sized, thinly myelinated Myelinated Internuclear Ophthalmoplegia fibers
  • Responsible for autonomic information
• Type-C fibers:
  • Unmyelinated nociceptive slow fibers (conduct at a rate of approximately 2 m/s)
  • Respond to combinations of thermal, mechanical, and chemical nociceptive stimuli

Types of Pain

Management of Pain

General principles

• Must be tailored to each patient’s circumstances, perspective, and physiologic condition
• Requires a systematic assessment and regular Regular Insulin reassessments:
  • Type: throbbing, cramping, burning, stabbing, etc ETC The electron transport chain (ETC) sends electrons through a series of proteins, which generate an electrochemical proton gradient that produces energy in the form of adenosine triphosphate (ATP). Electron Transport Chain (ETC).
  • Periodicity: continuous, with or without exacerbations or incident
  • Location
  • Intensity (may be determined with a visual analog scale Scale Dermatologic Examination)
  • Modifying factors
  • Effects of treatments
  • Functional impact
  • Impact on patient
• Whenever possible, use targeted, disease-specific treatment.
• Incorporate non-pharmacologic adjuncts and maximize the use of non-opioid analgesics before the use of opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics. 
• If an opioid Opioid Compounds with activity like opiate alkaloids, acting at opioid receptors. Properties include induction of analgesia or narcosis. Constipation is prescribed for pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways:
  • Use short-acting agents, when possible
  • Use for the shortest duration possible 
  • Screen for risk of opiate misuse:
    • Urine drug screening Screening Preoperative Care
    • Opioid Opioid Compounds with activity like opiate alkaloids, acting at opioid receptors. Properties include induction of analgesia or narcosis. Constipation Risk Tool (ORT)
  • Utilize local prescription monitoring program
  • Counsel patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship on safe storage and disposal

Management of chronic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways

The following principles are recommended by the World Health Organization (WHO) as a basis for the treatment of chronic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways:

• “By the clock”: Analgesics should be given at regular Regular Insulin intervals. The frequency depends on whether it is a long- or short-acting preparation. 
• “By the mouth”: If possible, drugs should be administered orally. If the oral route is not feasible, the least invasive route should be considered (e.g., sublingual or subcutaneous before IV). 
• “By the ladder”: Stick to the 3-step system (see figure below). Drug selection Selection Lymphocyte activation by a specific antigen thus triggering clonal expansion of lymphocytes already capable of mounting an immune response to the antigen. B cells: Types and Functions should be appropriate to the severity of the pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways. With severe pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, it may be appropriate to begin at the top of the ladder with a strong opioid Opioid Compounds with activity like opiate alkaloids, acting at opioid receptors. Properties include induction of analgesia or narcosis. Constipation. It is usually not necessary to step down unless the cause of pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways is believed to have resolved. 
• “By the individual with attention to details”: Dosing of pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways medication should be adapted to the individual, as every patient responds differently. To optimize adherence and outcomes, the patient and those who care for them should be provided with a written program.

Most commonly used substances

• Non-opioid medications
  • Nonsteroidal anti-inflammatory drugs ( NSAIDs NSAIDS Primary vs Secondary Headaches; ibuprofen Ibuprofen A nonsteroidal anti-inflammatory agent with analgesic properties used in the treatment of rheumatism and arthritis. Nonsteroidal Antiinflammatory Drugs (NSAIDs), naproxen Naproxen An anti-inflammatory agent with analgesic and antipyretic properties. Both the acid and its sodium salt are used in the treatment of rheumatoid arthritis and other rheumatic or musculoskeletal disorders, dysmenorrhea, and acute gout. Nonsteroidal Antiinflammatory Drugs (NSAIDs))
  • Acetaminophen Acetaminophen Acetaminophen is an over-the-counter nonopioid analgesic and antipyretic medication and the most commonly used analgesic worldwide. Despite the widespread use of acetaminophen, its mechanism of action is not entirely understood. Acetaminophen
  • Aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs)
• Weak opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics
  • Codeine Codeine An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. Opioid Analgesics 
  • Dihydrocodeine 
  • Tramadol Tramadol A narcotic analgesic proposed for severe pain. It may be habituating. Opioid Analgesics
• Strong opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics 
  • Morphine Morphine The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. Opioid Analgesics 
  • Oxycodone Oxycodone A semisynthetic derivative of codeine. Opioid Analgesics 
  • Methadone Methadone A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. Opioid Analgesics
  • Hydromorphone Hydromorphone An opioid analgesic made from morphine and used mainly as an analgesic. It has a shorter duration of action than morphine. Opioid Analgesics 
  • Oxymorphone
  • Buprenorphine Buprenorphine A derivative of the opioid alkaloid thebaine that is a more potent and longer lasting analgesic than morphine. It appears to act as a partial agonist at mu and kappa opioid receptors and as an antagonist at delta receptors. The lack of delta-agonist activity has been suggested to account for the observation that buprenorphine tolerance may not develop with chronic use. Opioid Analgesics
  • Fentanyl Fentanyl A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. Opioid Analgesics 
• Adjuvant Adjuvant Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (freund’s adjuvant, bcg, corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Vaccination analgesics (for specific indications)
  • Alpha-2 adrenergic agonists Adrenergic agonists Sympathomimetic drugs, also known as adrenergic agonists, mimic the action of the stimulators (î±, β, or dopamine receptors) of the sympathetic autonomic nervous system. Sympathomimetic drugs are classified based on the type of receptors the drugs act on (some agents act on several receptors but 1 is predominate). Sympathomimetic Drugs (e.g., clonidine Clonidine An imidazoline sympatholytic agent that stimulates alpha-2 adrenergic receptors and central imidazoline receptors. It is commonly used in the management of hypertension. Sympathomimetic Drugs, tizanidine Tizanidine Spasmolytics):
    • Augment the effect of opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics
    • Allow for reduction of opioid Opioid Compounds with activity like opiate alkaloids, acting at opioid receptors. Properties include induction of analgesia or narcosis. Constipation dosages in acute postoperative pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, chronic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, neuropathic pain Neuropathic pain Caused by lesion or disease affecting the nervous system (PNS or CNS). Pain: Types and Pathways
  • Anticonvulsants (e.g., gabapentin Gabapentin A cyclohexane-gamma-aminobutyric acid derivative that is used for the treatment of partial seizures; neuralgia; and restless legs syndrome. Second-Generation Anticonvulsant Drugs, phenytoin Phenytoin An anticonvulsant that is used to treat a wide variety of seizures. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. First-Generation Anticonvulsant Drugs, carbamazepine Carbamazepine A dibenzazepine that acts as a sodium channel blocker. It is used as an anticonvulsant for the treatment of grand mal and psychomotor or focal seizures. It may also be used in the management of bipolar disorder, and has analgesic properties. First-Generation Anticonvulsant Drugs, pregabalin Pregabalin A gamma-aminobutyric acid (gaba) derivative that functions as a calcium channel blocker and is used as an anticonvulsant as well as an anti-anxiety agent. It is also used as an analgesic in the treatment of neuropathic pain and fibromyalgia. Second-Generation Anticonvulsant Drugs):
    • Primarily used in neuropathic pain Neuropathic pain Caused by lesion or disease affecting the nervous system (PNS or CNS). Pain: Types and Pathways syndromes (e.g., trigeminal neuralgia Trigeminal neuralgia Trigeminal neuralgia (TN) is an often chronic and recurring pain syndrome involving the sensory distribution of the trigeminal nerve (cranial nerve (CN) V). The pain is typically unilateral and described as an acute, sharp, electric-shock-like pain involving the maxillary or mandibular areas and often associated with spasm of facial muscles. Trigeminal Neuralgia, peripheral neuropathy Neuropathy Leprosy)
    • May be useful as adjuvants in chronic nociceptive pain Nociceptive pain Dull or sharp aching pain caused by stimulated nociceptors due to tissue injury, inflammation or diseases. It can be divided into somatic or tissue pain and visceral pain. Pain: Types and Pathways syndromes (e.g., osteoarthritis Osteoarthritis Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis)
    • May be used as migraine Migraine Migraine headache is a primary headache disorder and is among the most prevalent disorders in the world. Migraine is characterized by episodic, moderate to severe headaches that may be associated with increased sensitivity to light and sound, as well as nausea and/or vomiting. Migraine Headache headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess prophylaxis Prophylaxis Cephalosporins
  • Antidepressants (e.g., tricyclics, serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS– norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS reuptake inhibitors ( SNRIs SNRIs Serotonin Reuptake Inhibitors and Similar Antidepressants)):
    • Primarily used in neuropathic pain Neuropathic pain Caused by lesion or disease affecting the nervous system (PNS or CNS). Pain: Types and Pathways syndromes (e.g., trigeminal neuralgia Trigeminal neuralgia Trigeminal neuralgia (TN) is an often chronic and recurring pain syndrome involving the sensory distribution of the trigeminal nerve (cranial nerve (CN) V). The pain is typically unilateral and described as an acute, sharp, electric-shock-like pain involving the maxillary or mandibular areas and often associated with spasm of facial muscles. Trigeminal Neuralgia, peripheral neuropathy Neuropathy Leprosy)
    • May be used as migraine Migraine Migraine headache is a primary headache disorder and is among the most prevalent disorders in the world. Migraine is characterized by episodic, moderate to severe headaches that may be associated with increased sensitivity to light and sound, as well as nausea and/or vomiting. Migraine Headache headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess prophylaxis Prophylaxis Cephalosporins
  • Beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers) (metopropolol, propanolol, timolol Timolol A beta-adrenergic antagonist that is similar in action to propranolol; the levo-isomer is more active. Timolol has been proposed as an anti-hypertensive, anti-arrhythmic, anti-angina, and anti-glaucoma agent. It is also used in the treatment of migraine disorders and tremor. Class 2 Antiarrhythmic Drugs (Beta Blockers)): may be used as migraine Migraine Migraine headache is a primary headache disorder and is among the most prevalent disorders in the world. Migraine is characterized by episodic, moderate to severe headaches that may be associated with increased sensitivity to light and sound, as well as nausea and/or vomiting. Migraine Headache headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess prophylaxis Prophylaxis Cephalosporins
  • Bisphosphonates Bisphosphonates Bisphosphonates are pyrophosphate analogs most well-known for treating osteoporosis by preventing bone loss. Bisphosphonates end in the suffix “-dronate” or “-dronic acid” (e.g., alendronate, risedronate, pamidronate) and bind to hydroxyapatite crystals in bone, inhibiting osteoclast-induced bone resorption. Bisphosphonates: may be used to treat cancer-related bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, osteoarthritis Osteoarthritis Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis
  • Botulinum toxin Botulinum toxin Toxic proteins produced from the species Clostridium botulinum. The toxins are synthesized as a single peptide chain which is processed into a mature protein consisting of a heavy chain and light chain joined via a disulfide bond. The botulinum toxin light chain is a zinc-dependent protease which is released from the heavy chain upon endocytosis into presynaptic nerve endings. Once inside the cell the botulinum toxin light chain cleaves specific snare proteins which are essential for secretion of acetylcholine by synaptic vesicles. This inhibition of acetylcholine release results in muscular paralysis. Botulism:
    • May be used to treat muscle spasticity Spasticity Spinal Disk Herniation → decreased spasticity-related pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
    • May be used to treat bruxism → decreased temporomandibular joint (TMJ)–related pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
    • May be used as migraine Migraine Migraine headache is a primary headache disorder and is among the most prevalent disorders in the world. Migraine is characterized by episodic, moderate to severe headaches that may be associated with increased sensitivity to light and sound, as well as nausea and/or vomiting. Migraine Headache headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess prophylaxis Prophylaxis Cephalosporins
  • Cannabis and cannabinoids Cannabinoids Cannabinoids are a class of compounds interacting with cannabinoid receptors. The 3 types of cannabinoids are phytocannabinoids (naturally derived from flora), endocannabinoids (endogenous), and synthetic cannabinoids (artificially produced). Cannabinoids (e.g., nabiximols, dronabinol Dronabinol A psychoactive compound extracted from the resin of cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (thc) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. Cannabinoids, nabilone Nabilone Cannabinoids):
    • Primarily used in cancer pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways syndromes
    • Some evidence of efficacy in neuropathic pain Neuropathic pain Caused by lesion or disease affecting the nervous system (PNS or CNS). Pain: Types and Pathways syndromes
  • Corticosteroids Corticosteroids Chorioretinitis:
    • Used as a short-term, potent antiinflammatory in several pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways syndromes
    • Used in the neurosurgical setting to treat headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess caused by increased intracranial pressure Intracranial Pressure Idiopathic Intracranial Hypertension
    • Used in the oncology setting to treat cancer-related bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways 
  • N-methyl-D-aspartate (NMDA) receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors antagonists ( ketamine Ketamine A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (n-methyl-d-aspartate receptors) and may interact with sigma receptors. Intravenous Anesthetics):
    • Primarily used as an adjuvant Adjuvant Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (freund’s adjuvant, bcg, corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Vaccination to treat perioperative pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
    • Some evidence of efficacy in neuropathic pain Neuropathic pain Caused by lesion or disease affecting the nervous system (PNS or CNS). Pain: Types and Pathways syndromes
  • Topical agents (e.g., lidocaine Lidocaine A local anesthetic and cardiac depressant used as an antiarrhythmic agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. Local Anesthetics, capsaicin, diclofenac Diclofenac A non-steroidal anti-inflammatory agent (nsaid) with antipyretic and analgesic actions. It is primarily available as the sodium salt. Nonsteroidal Antiinflammatory Drugs (NSAIDs) patch Patch Nonpalpable lesion > 1 cm in diameter Generalized and Localized Rashes, ketamine Ketamine A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (n-methyl-d-aspartate receptors) and may interact with sigma receptors. Intravenous Anesthetics cream, gabapentin Gabapentin A cyclohexane-gamma-aminobutyric acid derivative that is used for the treatment of partial seizures; neuralgia; and restless legs syndrome. Second-Generation Anticonvulsant Drugs cream): may be used to treat regional neuropathic pain Neuropathic pain Caused by lesion or disease affecting the nervous system (PNS or CNS). Pain: Types and Pathways

Approach to specific types of pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways