Nociception and Pain PDF

Nociception and pain Asghar Ghasemi Professor of Physiology Shahid Beheshti University of Medical Sciences  Today discussion 1 Pain definition and types 2 Painful stimuli 3 Pain receptors (nociceptors) 4 Nociception (pain transduction) 5 Pain conductin...

Nociception and pain Asghar Ghasemi Professor of Physiology Shahid Beheshti University of Medical Sciences  Today discussion 1 Pain definition and types 2 Painful stimuli 3 Pain receptors (nociceptors) 4 Nociception (pain transduction) 5 Pain conducting pathways 6 Gate control theory and analgesia system 7 Non-adapting nature of pain and hyperalgesia 8 Pain localization 9 Visceral pain 10 Headache Pain definition and types  Definition of pain Pain is defined as a complex collection of unpleasant sensory, emotional, and cognitive experiences associated with actual or potential tissue damage and manifested by certain autonomic, psychological, and behavioral reactions.  This definition tell us that: 1. Pain is sensory experience is accompanied by a usually 2. Pain is felt when body tissue is stimulated so strongly that there is danger of its destruction.  Pain… Unlike the other sensory modalities, pain contributes little to our knowledge of our surroundings. Pain informs us about threats to our bodies, from outside or within them. Pain and is thus necessary for a normal life Like the other senses, pain increases our chances of survival. Pain is one of the most common complaints in clinical medicine.  Paul Brand (pain expert): Pain is the gift that nobody wants. Pain qualities (submodalities ) Origins Fast vs. slow pain  Acute pain vs. chronic pain Acute pain (e.g., burning the skin) Is ordinarily limited to the damaged area We are quite certain where it originates The intensity of the pain is directly related to the intensity of the stimulus Indicates impending or actual tissue damage, and thus has a clear signal and warning function After the damage has been repaired it soon disappears  Acute pain vs. chronic pain Chronic pain Persist for a long time (e.g., back pain, the pain of tumors) or recur at more or less regular intervals (e.g., migraine headaches, heart pain in angina pectoris). These forms of pain (persistent and recurrent pain), together are called chronic pain In general pain is not regarded as "chronic" until it has lasted more than 6 months In the chronic pain, there is often no straightforward relation between the degree of organic damage and the intensity of the pain No physiological function can be ascribed to chronic pain Painful stimuli  Painful Stimuli Stimuli that have the potential to cause tissue damage can cause pain: 1. Mechanical 2. Thermal (skin temperature > 45 ° C or < 15 ° C) 3. Chemical agents Mechanical and thermal stimuli → Fast pain Mechanical, thermal, and chemical stimuli → Slow pain Painful Stimuli  Chemical agents that causes pain 1. Peptides Bradykinin Proteolytic enzymes (proteases) 2. Neurotransmitters Serotonin Histamine Norepinephrine ACh 3. Ions K+ H+ (acids) 4. Others ATP Capsaicin Pain receptors (nociceptors)  Pain receptors=nociceptors Nocieceptors are pseudounipolar neurons with free nerve endings Cell bodies are in DRG or trigeminal ganglion Peripheral processes are distributed throughout the body Central processes travel to the CNS  The liver capsule is extremely sensitive to both direct trauma and stretch, and the bile ducts are also sensitive to pain. In the lungs, both the bronchi and the parietal pleura are very sensitive to pain. In the brain, meninges, blood vessels, and tentorium are extremely sensitive to pain.  Polymodal nociceptors are the most common types of nociceptors Silent nociceptors are mostly found in the viscera and activated upon sensitization  4 Nociception  Nociception Nociception is the process by which intense (thermal, mechanical, or chemical) stimuli are detected by nociceptors Nociception (mechanical and thermal stimuli) Peripheral nociceptor terminal  Heat-pain receptors Non-nociceptiv e thermoreceptor s Cold-pain receptors  Nociception (chemical stimuli) Bradykinin might be the chemical agent GPCR: G-protein coupled receptors most responsible for causing pain after tissue damage G-protein Peripheral nociceptor PLC: Phospholipase C terminal PIP2: phosphatidyl inositol bis-phosphate IP3: Inositol triphosphate DAG: Diacylglycerol  Peripheral nociceptor terminal ASCI: acid-sensitive ion channels P2X: purinergic receptor Neurotransmitters of pain fibers  5 Pain-conducting pathways DCML AL Crude touch and pressure Pain and temperature  Paleo and neospinothalamic tracts Paleospinothalamic tract: for slow pain Neospinothalamic tract: for fast pain Details on dorsal horn Dorsal horn Phylogeny: the evolutionary history of a kind of organism and glutamate  6 Gate control theory and analgesia system  Pain-reducing strategies of the body 1. Analgesia system 2. Endogenous morphine-like substances (Endogenous opioids) Gate control theory of pain Tonically active SG (substantia gelatinosa) inhibitory interneuron= Enkephalin neuron Analgesia system PAG: of the brain and spinal cord suppress pain signals in both the cord and the brain stem  Endogenous opioid (Endorphins) Injection of minute quantities of morphine either into the periventricular nucleus around the third ventricle or into the PAG area of the brain stem causes an extreme degree of analgesia. Morphine-like agents, mainly the opiates, were found in the human body Endorphins: Endogenous morphine-like substances Precursor Opiate substance Distribution Proenkephalin Enkephalin Brain stem and spinal cord Pro-opiomelanocortin β-Endorphin Hypothalamus and the pituitary (POMC) gland Prodynorphin Dynorphin Brain stem and spinal cord (lower than enkephalin)  Analgesi a system PAG: Periaqueductal gray region LC: Locus coeruleus EnK: Enkephalin Transmitters that stimulate pain Transmitters that inhibit pain Glutamate Serotonin P substance Norepinephrine Enkephalin GABA  7 Non-adapting nature of pain and hyperalgesia  Non-adapting nature of pain receptors In contrast to most other sensory receptors of the body, pain receptors adapt very little and sometimes not at all. Under some conditions, excitation of pain fibers becomes progressively greater, especially for slow, aching, nauseous pain, as the pain stimulus continues (hyperalgesia). Failure of pain receptors to adapt it allows the pain to keep the person apprised of a tissue-damaging stimulus as long as it persists.  Hyperalgesia and allodynia Pain threshold: the stimulus intensity just high enough to produce a pain sensation  Two types of hyperalgesia Primary hyperalgesia Excessive sensitivity of the pain receptors – Extreme sensitivity of sunburned skin, which results from sensitization of the skin pain endings by local tissue products from the burn— perhaps histamine, prostaglandins, and others. Secondary hyperalgesia: Facilitation of sensory transmission – Secondary hyperalgesia frequently results from lesions in the spinal cord or the thalamus. – Herpes zoster (shingles) – Tic Douloureux (trigeminal neuralgia or glossopharyngeal neuralgia)  Herpes zoster Chickenpox a disease of childhood, is caused by the virus. It produces an itchy rash that usually clears up without complications. However, the virus, remains for life in the DRG. If the immune system is compromised, the virus can travel along the sensory nerve fibers by and cause Trigeminal neuralgia Is a syndrome characterized by recurring episodes of intense pain on one side of the face with painless intervals between attacks. It is caused by a nearby blood vessel, but sometimes a tumor, putting pressure on the trigeminal/glossopharyngeal nerves. It can be triggered by touch, toothbrushing, drinking, shaving, or face washing (i.e., mechanoreceptive stimulus rather than pain stimulus). The pain lasts from a few seconds to a minute or two, but may strike up to 100 times a day. It affects women more often than men, and usually strikes after age 50.  8 Pain localization  Fast pain localization The fast-sharp type of pain can be localized much more exactly than slow-chronic pain. However, when only pain receptors are stimulated, without the simultaneous stimulation of tactile receptors, even fast pain may be poorly localized, often only within 10 centimeters or so of the stimulated area. When tactile receptors that excite the DCML system are simultaneously stimulated, the localization can be nearly exact.  Slow pain localization Localization of pain transmitted via the paleospinothalamic pathway is imprecise. Slow-chronic pain can usually be localized only to a major part of the body, such as to one arm or leg but not to a specific point on the arm or leg. This is due to thee multisynaptic, diffuse connectivity of paleospinothalamic pathway and explains why patients often have serious difficulty in localizing the source of some chronic types of pain.  9 Visceral pain  Visceral pain The most important receptors in viscera are nociceptors Nociceptors for visceral pain are similar to those for somatic pain but have fewer numbers Viscera are lined with a two-layered membrane: – Visceral layer – Parietal layer = wall  Visceral pain: Parietal pain vs. true visceral pain True visceral pain Parietal pain associated with true visceral pain – Is pain from the parietal wall overlying a viscus – Is frequently sharp Example: a knife incision through the peritoneum is very painful, whereas a similar cut through the visceral peritoneum or through a gut wall is not very painful, if it is painful at all.  Causes of visceral pain Highly localized types of damage to the viscera seldom cause severe pain. For example, a surgeon can cut the gut entirely in two in a patient who is awake without causing significant pain. Conversely, any stimulus that causes throughout a viscus (e.g., ischemia) causes pain that can be severe.  Cramps Often, pain from a spastic viscus occurs in the form of with the pain increasing to a high degree of severity and then subsiding. This process continues intermittently once every few minutes. The intermittent cycles result from periods of contraction of smooth muscle. The cramping type of pain frequently occurs in persons with appendicitis, gastroenteritis, constipation, menstruation, parturition, gallbladder disease, or ureteral obstruction.  Referred visceral pain Origin: Viscera Referred to: Somatic structure (skin, muscle, bone) When visceral pain is referred to the surface of the body, the person generally localizes it in the dermatomal segment from which the visceral organ originated in the embryo, not necessarily where the visceral organ now lies.  Heart’ s visceral pain Heart originated in the neck and upper thorax Heart’ s visceral pain fibers pass Angina pectoris upward along the sympathetic sensory nerves and enter the spinal cord between segments C3 and T5. Pain from the heart is referred to the left side of the neck, over the shoulder, over the pectoral muscles, down the arm, and into the substernal area of the upper chest. These are the areas of the body surface that send their own somatosensory nerve fibers into the C3 to T5 cord segments. Visceral and parietal transmission of pain signals from the inflamed appendix (Appendicitis) Convergence theory for referred pain Convergence theory for referred pain  Characteristics of Visceral pain Visceral pain is – Diffuse in nature – Poorly localized – Associated with autonomic symptoms – Often referred to other structures  10 Headache  Headache Headaches are a type of pain referred to the surface of the head from deep head structures.  Headache Much or most of the pain of headache is not caused by damage in the brain itself because the brain tissues themselves are almost totally insensitive to pain. Conversely, tugging on the venous sinuses around the brain, damaging the tentorium, or stretching the dura at the base of the brain can cause intense pain that is recognized as headache. Almost any type of traumatizing, crushing, or stretching stimulus to the blood vessels of the meninges can cause headache. Migraine headache  Migraine headache The pain arises not from the brain tissue but from fibers of the trigeminal nerve that innervate the dura mater and cerebral arteries. Serotonin is a key mediator in the in its treatment. Thank you