Receptors in Skin Skin has three separate layers: Epidermis—outermost layer, thinnest Dermis—middle layer, contains nerve fibers Hypodermis anchors muscles and helps shape body. Sensory transduction—the conversion of electrical energy from a stimulus into a change in membrane potential in a receptor cell Receptor potentials (or generator potentials) are local changes in membrane potential.

The Structure and Function of the Pacinian Corpuscle as an example of transduction of mechanical to action potentials The Pacinian corpuscle (or lamellated corpuscle) is a skin receptor that detects vibration. A stimulus to the corpuscle produces a graded electrical potential. When the potential is big enough, the receptor reaches threshold and generates an action potential.

Properties of Skin Receptors Related to Touch Four tactile receptors detect touch: Pacinian corpuscles—vibration, fast-adapting Meissner’s corpuscles—touch, fast-adapting Merkel’s discs—touch, slow-adapting Ruffini’s endings—stretch, slow-adapting

Various Touch Receptors Responding to Braille

Table 8.2 Fibers That Link Receptors to the CNS

Somatosensory Pathways The dorsal column system delivers touch information to the brain. Receptors send axons via the dorsal column of the spinal cord where they synapse on dorsal column nuclei in the medulla. Axons from neurons in the medulla cross the midline and go to the thalamus. A dermatome is a strip of skin innervated by a particular spinal root. Adjacent dermatomes overlap a small amount.

Representation of the Body Surface in Somatosensory Cortex (Part 1) biopsych4e-fig-08-16-1.jpg

The Columnar Organization of the Somatosensory Cortex biopsych4e-fig-08-17-0.jpg

Doesn’t That Hurt? Pain—an unpleasant experience associated with tissue damage Congenital insensitivity to pain is an inherited syndrome where the person does not experience pain. Pain helps us to withdraw from its source, engage in recuperative actions, and to signal others.

The Multifaceted Character of Pain The McGill Pain Questionnaire describes three aspects of pain: Sensory—discriminative quality (e.g., throbbing, gnawing, shooting) Motivational—affective (emotional) quality (e.g., tiring, sickening, fearful) Cognitive evaluative quality (e.g., no pain, mild, excruciating)

Peripheral Mediation of Pain Nociceptors are peripheral receptors that respond to painful stimuli. Free nerve endings in the dermis have specialized receptor proteins. The free nerve endings respond to temperature changes, chemicals, and pain. Capsaicin—the chemical that makes chili peppers “hot” The receptor that binds capsaicin is the transient receptor potential vanilloid type1 (TRPV1), or vanilloid receptor 1. This receptor normally detects painful heat.

Receptors That Detect Pain and Temperature Capsaicin—the chemical that makes chili peppers “hot” The receptor that binds capsaicin is the transient receptor potential vanilloid type1 (TRPV1), or vanilloid receptor 1. This receptor normally detects painful heat. The TRP2 receptor differs from TRPV1: Detects even higher temperatures Does not respond to capsaicin Is found on Aδ fibers—large myelinated axons that register pain quickly TRPV1 receptors are on C fibers—thin unmyelinated axons that conduct slowly, producing lasting pain. The cool-menthol receptor 1 (CMR1) responds to menthol and to cool temperatures—located on C fibers. Other free nerve endings respond to histamine and use gastrin-releasing peptide (GRP) to stimulate neurons to provide the sensation of itch. The gene SCN9A (or Nav1.7) encodes a sodium channel which may represent the specific pain receptor protein.

Pain ascends the spinothalamic system to reach the brain The anterolateral, or spinothalamic, system transmits the sensations of pain and temperature. Free nerve endings synapse on spinal neurons in the dorsal horn. Pain information crosses the midline in the spinal cord, before ascending to the thalamus. Peripheral fibers probably use glutamate to excite spinal cells in the dorsal horn. They also release substance P, a neuropeptide. Postsynaptic neurons take up substance P and remodel dendrites, which may affect pain perception. Synapse here

Ascending and Descending Pain Pathways The periaqueductal gray (PAG) is an area in the midbrain involved in pain perception; stimulation of the PAG produces potent analgesia. Pain information can be blocked by a gating action in the spinal cord. Pain information is integrated in the cingulate cortex. Different subregions of the cingulate cortex are activated if a person is experiencing the pain or is empathizing with another

Pain Pathways STATE-DEPENDENT OPIOID CONTROL OF PAIN Fields et al Nature Neuroscience Reviews VOLUME 5, 565-575 2004 Filelds et al Nature NeuroscienceReviews 2004

Types of Pain Relief Intervention Analgesia—the loss of pain sensation Opiates are drugs that control pain. Opioids are endogenous opiate-like peptides in the brain. Three classes of endogenous opioids are endorphins, enkephalins and dynorphins. Opioid receptors respond to opiates or opioids. Caution is often taken when prescribing opiates for pain, due to risk of addiction. However, it appears that most people who become addicted from pain prescriptions were already drug abusers. Marijuana can be an analgesic and works by stimulating endogenous cannabinoid receptors (CB1 receptors). Transcutaneous electrical nerve stimulation (TENS) delivers electrical pulses to the skin. TENS relieves pain by stimulating the nerves around the source of the pain. Naloxone is an opioid antagonist that can block the analgesic effect of TENS. A placebo can sometimes relieve pain, even though it is an inert substance, probably by releasing endogenous opiates. Acupuncture relieves pain by inducing endorphin release. Stress can activate analgesia systems.

Social Rejection Activates Brain Regions for Affective Pain Social rejection activates the anterior cingulate cortex, and the extent to which a person is upset by rejection correlates with activation of this region. The more distress or feelings of rejection subjects feel, the greater the activity in anterior cingulate cortex.

Placebo effects terminology Placebo is Latin for “I will please” An inert substance or treatment that does not have a direct physiological effect The original meaning: 1950: The effect of a placebo treatment The alternative meaning: 1960-80: The effect of the interaction between the patient and the health provider Belief in the beneficial nature of the treatment a key component of the true placebo effect enhanced by factors such as interaction with the physician sensory impact of the treatment Negative beliefs can generate a nocebo effect may explain some psychogenic illnesses basis of much research in psychoneuroimmunology

Placebos have effect on Placebo Effects Placebos have effect on subjective and objective outcomes in a large proportion of patients with a wide range of clinical conditions such as Pain Asthma Survival after myocardial infarction Hypertension Colds Used in research trials to objectively test the efficacy of new treatments One group is given the treatment, while another group (the control group) receives a placebo Comparing the results from both groups should reveal the effects of the treatment

Placebo Response Mechanisms Examples of pain relief “analgesia” from placebo Expectation “belief” in treatment Activation of opiate based descending control system 30 – 50 % get some analgesia can be blocked by naloxone an opiate antagonist Expectation produces increased activity during anticipation of pain in the prefrontal cortex Decreased activity in the thalamus, insula, and anterior cingulate cortex Probably a frontal cortex activation of areas in the cingulate cortex which then activates the PAG midbrain areas

Placebo Response Mechanisms Expectation from: Conditioning: previously experiencing the benefit Social learning: observing others produces similar placebo responses to conditioning Verbal suggestions: alone produces smaller effects Problem of no “untreated”control group effect consists of two components nonspecific effects (eg, natural recovery) a "true placebo effect" that is the psychological therapeutic effect of the treatment So effect of placebo is not isolated from spontaneous remission regression to the mean other factors