PAIN AND ANALGESIC PHARMACOLOGY

Slides:



Advertisements
Similar presentations
Pathophysiology of Pain
Advertisements

Neuroanatomy/Pain Review
Somatosensory perception: Touch, pain and analgesia
1 Pain. 2 Types of Pain Acute Pain Acute Pain –Complex combination of sensory, perceptual, & emotional experiences as a result of a noxious stimulus –Mediated.
Managing Pain With Therapeutic Modalities
# Lab 3#. Introduction - Pain: an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms.
OPIOIDS NIRALI PATEL (2009) Medical University of Sofia, Faculty of Medicine Department of Pharmacology and Toxicology.
Pharmacologic Treatment of Post-Herpetic Neuralgia (PHN)
Transcutaneous Electrical Nerve Stimulation (TENS)
ESAT 3640 Therapeutic Modalities
Nursing Care of Clients Experiencing Pain. Pain Pathway A-delta fibers: transmit pain quickly, associated with acute pain C-fibers: transmit pain more.
Copyright © 2015 Cengage Learning® 1 Chapter 19 Analgesics, Sedatives, and Hypnotics.
Chronic Pain. What is pain? A sensory and emotional experience of discomfort. Single most common medical complaint.
how the brain receives and interprets information from the environment
Hand out has most everything I want you to know on it
Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins Chapter 35 Somatosensory Function, Pain, and Headache.
Dr Abdulrahman Alhowikan Collage of medicine Physiology Dep.
Brain Analgesia System Dr Ghulam Mustafa Learning objectives What is brain analgesia system Enlist components of analgesia system Enlist chemical mediators.
Pain and Analgesia PAIN IS
PAIN !!! DENT/OBHS 131 Neuroscience Pain…. Is a submodality of somatosensation Is the perception of unpleasant or aversive stimulation (sensory.
Assisted Professor Basic Science Department 2012
NRSC/SP H 282 October 9, 2006 PAIN. Step on a thumbtack?
Sensory Nervous System Week 11 Dr. Walid Daoud A. Professor.
Chronic pain Sai Yan Au. Chronic Pain  Definition  Causes and mechanisms of chronic pain  Effects of chronic pain  Assessment and evaluation  Management.
UNIVERSITY OF GUYANA BMP 3201 PAIN ASSIGNMENT 1
Assessing Pain By Orest Kornetsky.
PAIN MODULATION Prof. Ashraf Husain MODULATION Pain modulation means pain perception variability which is influenced by endogenous and exogenous mechanism.
Pain Pain: is a subjective sensation that accompanies the activation of nociceptors which signals actual or potential tissue damage. Pain is stimulated.
The Nervous System CNS BrainSpinal cord PNS Sensory division (afferent) Motor division (efferent) Somatic nervous system (voluntary) Autonomic nervous.
PHYSIOLOGY, MECHANISMS, BIOCHEMISTRY & MANAGEMENT- by wurl boss Neil Barry ALL ABOUT BEADS PAIN.
Local Anaesthesia: Neurophysiology Pain : Pain : –An unpleasant sensory and emotional experience associated with actual or potential tissue damage. –Two.
Chronic Pain. What is pain? A sensory and emotional experience of discomfort. Single most common medical complaint.
Nociceptive sensation. Somatic sensory analyzer
Pain Modulaton Stopping the Hurt Pain Modulaton Stopping the Hurt.
The Neurobiology of Pain. What is Pain? Pain is part of the body's defense system. The reflex reaction to escape painful stimulus is meant to adjust behavior.
Pain Management. Key Points Pain is an unpleasant sensation, usually associated with disease or injury. A.Transmission 1.Stimulation of neurons (pain.
UNIT VII: PAIN. Objectives: By the end of this lecture the students will be able to : Review the concept of somatosensory pathway. Describe the function.
The Ascending Tracts of the Spinal Cord Lufukuja G.1.
The Nature & Symptoms of Pain Chapter 11. Qualities & Dimensions of Pain Organic pain vs. Psychogenic pain Acute vs. Chronic Pain.
Pain Theories Specificity –Separate sensory modality Pattern –Different patterns of activity in neural networks Gate-control.
Pain Management. What is Pain? How do you define pain? Is pain consistent? Can you always tell how much pain someone is in? How do you manage pain?
NEUROPHYSIOLOGY of Pain
PHT 222 – UNIT – 4 – TENS - QUIZ. TRUE OR FALSE  TENS is the application of E.S. to the skin via surface electrodes to stimulate nerve (Sensory) fibers.
Chronic Pain in Alkaptonuria Andrew Jones, Liverpool and Wirral.
بنام آنكه جان را فكرت آموخت. Neurochemistry of Pain Sensation References: - Essentials of Pain Medicine (Benzon) - Principles of neural science (Kandel)
ANALGESIC DRUGS # PHL 322, Lab. 3#.
© UWCM/SONMS/Pain/MJohn
List Three Mechanisms by which Chronic Opioid Therapy Can Worsen Pain
PAIN MANAGEMENT.
How the number of learning trials affects placebo and nocebo responses
بنام آنكه جان را فكرت آموخت
Pain Modulation Pain Transmission
Pharmacology ii Tutoring
Pain systems Domina Petric, MD.
Conduction speed.
PAIN and its MANAGEMENT
The Nature & Symptoms of Pain
بنام آنكه جان را فكرت آموخت
12-7 Synapses Synaptic Activity Action potentials (nerve impulses)
Comfort Ch 41.
Pathophysiology of Pain,Classification and Treatment
Neuropathic Pain: Principles of Diagnosis and Treatment
School of Pharmacy, University of Nizwa
School of Pharmacy, University of Nizwa
Done by Abdallah Ayyoub
Pain Modulation Editing file Objectives: Done by :
PAIN MANAGEMENT Tasneem Anagreh.
بسم الله الرحمن الرحيم.
Pain management Done by : Sudi maiteh.
Presentation transcript:

PAIN AND ANALGESIC PHARMACOLOGY

Pain is an unpleasant sensory and emotional experience that serves to alert an individual to actual or potential tissue damage. This damage can be caused by exposure to noxious chemical, mechanical, or thermal stimuli (e.g., acids, pressure, percussion, and extreme heat) or by the presence of a pathologic process (e.g., a tumor, muscle spasm, inflammation, nerve damage, organ distention, or other mechanism that activates nociceptors on sensory neurons). Although pain serves a protective function by alerting a person to the presence of a health problem, its non- restrained expression often leads to considerable morbidity and suffering. For this reason, analgesics or drugs that relieve pain are used for symptomatic treatment of pain from a wide variety of disease states, ranging from acute and chronic physical injuries to terminal cancer.

Based on their mechanisms of action, analgesics can be classified as opioid analgesics or nonopioid analgesics. Opioid analgesics act primarily in the spinal cord and brain to inhibit the neurotransmission of pain. In contrast, nonopioid analgesics act primarily in peripheral tissues to inhibit the formation of algogenic or pain-producing substances such as prostaglandins. Because most of the nonopioid analgesics also exhibit significant antiinflammatory activity, they are called nonsteroidal antiinflammatory drugs (NSAIDs).

To facilitate the selection of an appropriate analgesic or anesthetic medication, patients are usually asked to describe their pain in terms of its intensity, duration, and location. In some cases patients report an intense, sharp, or stinging pain. In other cases they describe a dull, burning, or aching pain. These two types of pain are transmitted by different types of neurons and their primary afferent fibers. Pain can be further distinguished on the basis of whether it is somatic, visceral, or neuropathic in origin. Somatic pain is often well localized to specific dermal, subcutaneous, or musculoskeletal tissue. Visceral pain originating in thoracic or abdominal structures is often poorly localized and may be referred to somatic structures. For example, cardiac pain is often referred to the chin, neck, shoulder, or arm. Neuropathic pain is usually caused by nerve damage, such as that resulting from nerve compression or inflammation, or from diabetes. Neuropathic pain is characteristic, for example, of trigeminal neuralgia (tic douloureux), postherpetic neuralgia, and fibromyalgia.

PAIN PATHWAYS Exposure to a noxious stimulus activates nociceptors on the peripheral free nerve endings of primary afferent neurons. The cell bodies of these neurons sit alongside the spinal cord in the dorsal root ganglia and send one axon to the periphery and one to the dorsal horn of the spinal cord. With noxious stimulation, substance P, glutamate, and other excitatory neurotransmitters are released from the central terminations of the primary afferent fibers onto neurons of the spinal cord. Many of these terminals synapse directly on spinothalamic tract neurons in the dorsal horn, which send long fibers up the contralateral side of the spinal cord to transmit pain impulses via ascending pain pathways to the medulla, midbrain, thalamus, limbic structures, and cortex.

The primary afferent fibers transmitting nociceptive information are Aδ fibers and C fibers, which are responsible for sharp pain and dull pain, respectively. Spinal reflexes activated by these fibers can lead to withdrawal from a noxious stimulus before pain is perceived by higher structures. Ascending pain pathways consist of two main anatomic-functional projections: the sensory discriminative component, to the cerebral cortex, and the motivational-affective component, to the limbic cortex. Projections to the sensory cortex alert an individual to the presence and anatomic location of pain, whereas projections to limbic structures (e.g., the amygdala) enable the individual to experience discomfort, suffering, and other emotional reactions to pain.

The activation of spinothalamic neurons in the spinal cord is modulated by descending inhibitory pathways from the midbrain and by sensory Aβ fibers arising in peripheral tissues. These two systems constitute the neurologic basis of the gate-control hypothesis. According to this hypothesis, pain transmission by spinothalamic neurons can be modulated, or gated, by the inhibitory activity of other types of large fibers impinging on them. The activation of spinothalamic neurons is inhibited by peripheral Aβ sensory fibers that stimulate the release of met-enkephalin from spinal cord interneurons. The Aβ fibers are thought to also mediate the analgesic effect produced by several types of tissue stimulation, including acupuncture and transcutaneous electrical nerve stimulation(TENS). These mechanisms explain the pain relief that may be produced by simply rubbing or massaging a mildly injured tissue.

The descending inhibitory pathways arise from periaqueductal gray (PAG) in the midbrain, and they project to medullary nuclei that transmit impulses to the spinal cord. The medullary neurons include serotonergic nerves arising in the nucleus magnus raphe (NMR) and noradrenergic nerves arising in the locus ceruleus (LC). When these nerves release serotonin and norepinephrine in the spinal cord, they inhibit dorsal spinal neurons that transmit pain impulses to supraspinal sites. Nerve fibers from the PAG also activate spinal interneurons that release an endogenous opioid peptide, met-enkephalin. The enkephalins act presynaptically to decrease the release of pain transmitters from the central terminations of primary afferent neurons. They also act on postsynaptic receptors on spinothalamic tract neurons in the spinal cord to decrease the rostral transmission of the pain signal. Opioid analgesics activate the descending PAG, NMR, and LC neuronal pathways, and they also directly activate opioid receptors in the spinal cord.

Opioid Agonists Opiates are drugs obtained from opium, a derivative of the poppy plant. Opiates have been used to treat pain for over 200 years. Opioid agonists mediate their effects at three types of opioid receptors: μ (mu) opioid receptors, δ (delta) and kappa (κ). There are three major families of endogenous opioid peptides: enkephalins, β-endorphins, and dynorphins.

Mechanism of Action The opioid receptors are prominent members of the G protein–coupled receptor superfamily. Activation of opioid receptors leads to inhibition of adenylyl cyclase and a decrease in the concentration of cyclic adenosine monophosphate an increase in K+ conductance, and a decrease in Ca2+ conductance . These actions cause both presynaptic inhibition of neurotransmitter release such as glutamate and substance P from the central terminations of small-diameter primary afferent fibers and postsynaptic inhibition of membrane depolarization of dorsal horn nociceptive neurons.

NSAIDs

TREATMENT OF NEUROPATHIC PAIN Neuropathic pain is the severe, debilitating, chronic pain that occurs in conditions such as trigeminal neuralgia, diabetic neuropathy, postherpetic neuralgia and phantom limb pain, affecting millions of people worldwide. It is often stated that neuropathic pain is opioid- resistant. However, clinical studies have shown opioids such as morphine, oxycodone, levorphanol, tramadol and tapentadol to be effective in the treatment of neuropathic pain, provided an adequate dose can be reached that provides analgesia without excessive side effects. The monamine uptake inhibiting properties of tramadol and tapentadol may contribute to their effectiveness.

Tricyclic antidepressants, particularly amitriptyline, nortriptyline and desipramine are widely used. These drugs act centrally by inhibiting noradrenaline reuptake and are highly effective in relieving neuropathic pain in some, but not all, cases. Their action is independent of their antidepressant effects. Drugs such as duloxetine and venlafaxine, which inhibit serotonin and noradrenaline uptake, are also effective and have a different side effect profile, but selective serotonin reuptake inhibitors show little or no benefit. Gabapentin and its congener, pregabalin, are antiepileptic drugs that are also effective in the treatment of neuropathic pain. They reduce the expression of α2δ subunits of voltage-activated calcium channels on the nerve membrane and reduce neurotransmitter release. The α2δ subunits are upregulated in damaged sensory neurons, thus explaining why these agents are more effective across a range of pain states associated with nerve damage than in other forms of pain.

Carbamazepine, another type of antiepileptic drug, is effective in trigeminal neuralgia but evidence for effectiveness against other neuropathic pains is lacking. Carbamazepine blocks voltage-gated sodium channels being slightly more potent in blocking Nav1.8 than Nav1.7 and Nav1.3 channels; all of these channel subtypes are thought to be upregulated by nerve damage and contribute to the sensation of pain. At higher concentrations, it inhibits voltage-activated calcium channels. Other antiepileptic agents such as valproic acid, lamotrogine, oxcarbazepine and topiramate, may have efficacy in some neuropathic pain states. Lidocaine (lignocaine), a local anaesthetic drug, can be used topically to relieve neuropathic pain. It probably acts by blocking spontaneous discharges from damaged sensory nerve terminals.

TREATMENT OF FIBROMYALGIA Fibromyalgia is a chronic disorder characterized by widespread musculoskeletal pain, fatigue and insomnia. Its cause is unknown, with no obvious characteristic pathology being apparent. It is associated with allodynia. As with neuropathic pain, classical analgesics (i.e NSAIDs and opioids), while bringing some relief, are not very effective in treating this disorder. Various antidepressant drugs (e.g. amitriptyline, citalopram, milnacipram, duloxetine, venlafaxine), antiepileptic agents (e.g. gabapentin, pregabalin), benzodiazepines (e.g. clonazepam, zopiclone) are currently used for this disorder – this long list reflecting their uncertain efficacy.