Pleasant to the Touch Patrick CARROLL, INSERM U1051 Institute des Neurosciences de Montpellier (INM)

Literary allusions to the sense of touch “Third: I cannot demonstrate it, but it seems to me, that in the whale the sense of touch is concentrated in the tail; for in this respect there is a delicacy in it only equalled by the daintiness of the elephant's trunk.” Moby Dick – Hermann Melville “Touch comes before sight, before speech. It is the first language and the last, and it always tells the truth.” Margaret Atwood “Don't touch me! Don't question me! Don't speak to me! Stay with me!” Waiting for Godot - Samuel Beckett “See how she leans her cheek upon her hand. O that I were a glove upon that hand That I might touch that cheek!” Romeo & Juliet – William Shakespeare

What is the sense of touch? - the faculty by which external objects or forces are perceived through contact with the body (especially the hands)

Touch skin mechanotransduction The Senses SENSE ORGAN Touch skin mechanotransduction Taste tongue Vision eye Hearing ear (cochlea) mechanotransduction Smell nose Balance ear (vestibule) mechanotransduction Temperature skin Pain skin Kinesthetic sense muscle & joints mechanotransduction (proprioception)

Somesthesia – faculty of body sensation Somatosensory system = perception of the environment Sensory modalities: Thermoception (temperature) Mechanoception (touch) Proprioception (muscle and joints) Nociception (pain) 5

Thermoception Nociception Mechanoception Proprioception Information is transmitted from body surface to nervous system by nerve cells - neurons Skin Thermoception Nociception Mechanoception Proprioception So I will present my project « Dev & … » that I am conducting at the Institu des Neurosciences Montpellier Muscle spindle

Sensory neurons are situated in ganglia beside the spinal cord

Sensory information is transmitted as electrical signals by nerve cells Sensory neurons are among the longest cells in the human body - up to 1.3 m.

Somesthesia – faculty of body sensation Somatosensory system = perception of the environment Sensory modalities: Thermoception (temperature) Mechanoception (touch) Proprioception (muscle and joints) Nociception (pain) 9

Touch neurons tell us WHERE and WHAT ……………

SOME FACTS ABOUT TOUCH You have more pain nerve endings than any other type. 2. The least sensitive part of your body is the middle of your back. 3. The most sensitive areas of your body are your hands, lips, face, neck, tongue, fingertips and feet. 4. There are about 100 touch receptors in each of your fingertips.

Congenital Insensitivity to Touch – no genes known at present Insensitivity to Touch – caused by viral disease or nerve damage - Loss of touch sensation Congenital Insensitivity to Pain (CIP) - Rare Genetic diseases - Loss of pain sensation Risk of injury Due to mutation in genes involved in development or neural transmission in neurons in pain circuits examples: NGF (nerve growth factor) TrkA (tyrosine kinase receptor for NGF) Sodium channels (NaV1.7)

Why is sense of touch important? Touch neurons enable us to « feel » TEXTURE, WEIGHT of objects Touch enable us to use TACTILE SCREENS Smartphones iPADS

Haptic perception - recognizing objects through touch. It involves a combination of somatosensory perception of patterns on the skin surface (e.g., edges, curvature, and texture) and proprioception of hand position and conformation

How does it work? Touch neurons in skin give feedback to motor neurons that control muscles retro-contrôle

What happens when it doesn’t work? Patients have loss of touch sensation, aberrant sensations dysthesias, parasthesias ……….. Consequences: severe handicap loss of fine motor control need to use vision as cue will fall down if they close their eyes (loss of posture control) mechanisms of neuropathic chronic pain

Active touch – Braille

Active touch Rodent “whisking” – rodents explore their environment using whiskers Rats are expert at navigating the world in the dark using their sense of touch. They rhythmically brush and tap about 60 large vibrissae (whiskers) against objects to determine object size, shape, orientation, and texture. This behavior is called “whisking.” Whiskers have no sensors along their length; instead, all mechanosensory information is detected by mechanosensory neuron terminals in the follicle at the whisker base.

Topographic representation of whiskers in the somatosensory cortex

Star-nosed mole (Taupe) Active touch – exploring the environment Star-nosed mole (Taupe)

Star-nosed Mole lives underground blind senses prey using touch with specialised sensory organ

Why is touch important? Postural reflexes Fine motor control 3. Exploration of the environment – haptic sense. 4. Social bonding

Neurons for « pleasant » touch? Slow conducting neurons for Pain and Temperature Håkan Olausson (Gothenburg, Sweden) Discovered neurons for « pleasant touch » during examination of a patient who lost the sense of normal touch. Low-threshold C-fibres

Neurons for « pleasant » touch – social bonding ?

Clinical aspects Touch : loss of fine motor control, posture, reflexes ….. Proprioception: loss of balance, loss of motor coordination …. Nociception: chronic pain, aberrant sensations Causes: peripheral neuropathies, demyelinating diseases, myopathies, nerve damage, viral infections, chronic inflammation ……..

Why is touch important? Prosthetic devices

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Specific types of mechanosensory stimulation are transduced by specific types of receptor cells.

RA SA very RA SA

Information from body surface is transmitted to spinal cord and then to the brain

Neural processing of sensory input occurs at specialized locations in the brain.

Somatic sensation – felt in skin, bones, tendons, and joints These sensations give rise to sensations of touch, pressure, body position awareness of movement, temperature and pain Visceral sensation – from the same types of receptors for somatic sensation in body organs

Figure 7-20 Somatosensory areas in the cortex of the brain are anatomically organized in relation to the source of information, with larger areas dedicated to parts of the body that process fine discriminations.

Different functional types of somatosensory neurons project to different regions of the spinal cord II III IV V Proprioceptive Mechanoceptive Thermonociceptive Moelle épinière Diversité fonctionelle Diversité de sites de projection centrales & périphériques La perception de la forme et de la texture des objets et la réponse aux mouvements de la peau et aux vibrations résultent de l’activation des mécanorécepteurs des ganglions rachidiens dorsaux. Les mécanorécepteurs peuvent être classés selon la morphologie de leurs organes de terminaison périphériques en disques de Merkel, en corpuscules de Ruffini, en corpuscules de Pacini, en corpuscules de Meissner et en terminaisons longitudinales lancéolées selon que la peau soit glabre ou poilue. La peau glabre contient les disques de Merkel et les corpuscules de Meissner tandis que la peau poilue possède les disques de Merkel et les terminaisons longitudinales lancéolées qui sont associés aux follicules pileux de protection. Les corpuscules de Meissner, les corpuscules de Pacini sont des récepteurs à adaptation rapide (RA). Les disques de Merkel sont des récepteurs à adaptation lente (SA). Meissner : adaptation rapide de type I (frisson) Pacini : adaptation rapide de type II (vibration). Merkel : adaptation lente de type I (toucher fin, texture) Ruffini : adaptation lente de type II (pression) Fibres mécanoréceptrices Aβ et C : toucher, vibration et frisson. Image modifiée de Marmigère & Ernfors.,2006

A reflex arc.

Flexion Reflex: Withdrawal from Painful Stimuli Figure 13-8: Flexion reflex and the crossed extensor reflex

Why is mechanoception/touch important? Postural reflexes Fine motor control 3. Neuropathic pain can be due to dysfunction of touch sensing neurons.

THANK YOU! Pleasant to the Touch Patrick CARROLL, INSERM U1051 Institute des Neurosciences de Montpellier (INM)

Why is touch important? Prosthetic devices

Dorsal root ganglion (DRG) Spinal cord Dorsal root ganglion (DRG) Proprioceptors TrkC/NT-3 Mechanoreceptors TrkB/BDNF AIM OF MY PROJECT IS: The neurons of the dorsal root ganglion are the first relay in the somato-sensory system. The sensory neurons of the DRG allow us to perceive signals from environment. The cell bodies of these neurons are situated in the spinal ganglion along the spinal cord. Different sub-types of sensory neurons are responsable for different sensory modalities e.g. nocicpetors … Specific subtypes of neurons, that innervate different peripheral targets send information to the spinal cord. Thus, the muscle proprioceptors ….. Etc. Myelinated, large-diameter cell bodies etc. Neurotrophic factor requirements …. The nociceptors sense noxious stimuli which are percieved as pain. Their axons are unmyelinated or thinly myelinated. The different types of sensory neurons project to different regions of the spinal cord 1. Find molecular markers to help us to understand physiology 2. Molecular changes after lesion of the a peripheral nerve…… since this type of nerve injury can lead to several pathological conditions such as … To do this, we have establisehd a multidisciplinary approach combining molecular analysis with physiological analyses in intereaction with F. Scamps group. I will show you an example of this approach before exposing the main project. The establishment of this system involves a complex interplay between specification factors, neurotrophic factors that regulate the survival and differentiation of these neurons, transcription factors that regulate targeting of central processes …. Nociceptors Thermoceptors TrkA/NGF Ret/GDNF

Proprioceptive sensory neurons provide constant feedback to the motor system

SA RA SA RA

Great functional diversity of somatosensory neurons electrophysiological properties, ion channels, peptides myelination, growth factor requirements

“Touch. It is touch that is the deadliest enemy of chastity, loyalty, monogamy, gentility with its codes and conventions and restraints. By touch we are betrayed and betray others ... an accidental brushing of shoulders or touching of hands ... hands laid on shoulders in a gesture of comfort that lies like a thief, that takes, not gives, that wants, not offers, that awakes, not pacifies. When one flesh is waiting, there is electricity in the merest contact.” Angle of Repose – Wallace Stegner