A nociceptor is a sensory receptor that sends signals that cause the perception of pain in response to potentially damaging stimulus. In a Sensory system, a sensory receptor is a structure that recognizes a stimulus in the internal or external environment of an Organism. Pain, in the sense of physical pain, is a typical sensory experience that may be described as the unpleasant awareness of a noxious stimulus or bodily harm Nociceptors are the nerve endings responsible for nociception, one of the two types of persistent pain (the other, neuropathic pain, occurs when nerves in the central or peripheral nervous system are not functioning properly). A nerve is an enclosed cable-like bundle of peripheral Axons (the long slender projections of Neurons. Nociception (synonym nociperception is defined as "the neural processes of encoding and processing Noxious stimuli. Neuropathy is a medical term usually short for Peripheral neuropathy. In Vertebrates the central nervous system ( CNS) is the part of the Nervous system which is enclosed in the Meninges. The peripheral nervous system ( PNS) resides or extends outside the Central nervous system (CNS which consists of the Brain and Spinal cord. Nociceptors are silent receptors and do not sense normal stimuli. Only when activated by a threatening stimulus do they invoke a reflex. A reflex action, also known as a reflex, is an involuntary and almost instant movement in response to stimulus.

Contents 1 History 2 Location 3 Development 4 Types and functions 4.1 Thermal 4.2 Mechanical 4.3 Chemical 4.4 Sleeping/silent 5 Pathway 6 Sensitivity 7 Nociceptors in non-mammalian animals 8 Terminology 9 See also 10 References

History

Nociceptors were discovered by Charles Scott Sherrington in 1906. Sir Charles Scott Sherrington OM, GBE, PRS ( November 27, 1857 - March 4, 1952) was an English neurophysiologist At the time it was believed that animals were mechanical devices that transformed sensory stimuli into motor responses. That transitioned into more specific research where it was determined that different types of stimulation to a receptive field led to different responses. One of these stimuli had an intensity and quality sufficient to trigger autonomic reflex withdrawal, and pain. Sherrington used many different styles of experiments to discover that this pain was a nociceptive reaction and was sensed through specific receptors called nociceptors. ^[1]

Location

In mammals, nociceptors are sensory neurons that are found in any area of the body that can sense pain either externally or internally. Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information External examples are in tissues such as skin (cutaneous nociceptors), cornea and mucosa. Tissue is a cellular organizational level intermediate between cells and a complete organism The skin is the outer covering of living tissue of an animal (or plant A cutaneous receptor is a type of Sensory receptor found in the dermis or epidermis The cornea is the transparent front part of the Eye that covers the iris, Pupil, and Anterior chamber. The mucous membranes (or mucosae; singular mucosa) are linings of mostly endodermal origin covered in Epithelium, which are involved in Internal nociceptors are in a variety of organs, such as the muscle, joint, bladder , gut and continuing along the digestive tract. Muscle (from Latin musculus, diminutive of mus "mouse" is contractile tissue of the body and is derived from the A joint is the location at which two or more Bones make contact In Anatomy, the urinary bladder is a hollow muscular, and distensible (or elastic organ that sits on the Pelvic floor in Mammals It is the The cell bodies of these neurons are located in either the dorsal root ganglia or the trigeminal ganglia. In Anatomy and Neurology, the dorsal root Ganglion (or spinal ganglion) is a nodule on a Dorsal root that contains cell bodies of The trigeminal nerve (the fifth Cranial nerve, also called the fifth nerve or simply V) is responsible for sensation in the face ^[2] The trigeminal ganglia are specialized nerves for the face, whereas the dorsal root ganglia associate with the rest of the body. The axons extend into the peripheral nervous system and terminate with the dendrites wherever a receptive field is found.

Development

Nociceptors develop from neural crest stem cells. The neural crest, a transient component of the Ectoderm, is located in between the Neural tube and the epidermis (or the free margins of the Neural folds The neural crest is responsible for a large part of early development in vertebrates. More specifically it is responsible for neuronal development. The neural crest stem cells form the neural tube and nociceptors grow from the dorsal part of this tube. In the developing vertebrate the neural tube is the Embryo 's precursor to the Central nervous system, which comprises the Brain and Spinal cord They form late during neurogenesis. If they were formed early they would be either proprioceptors or low-threshold mechanoreceptors. Proprioception (ˌproʊpriːəˈsɛpʃən PRO -pree-o-SEP-shun from Latin proprius, meaning "one's own" and perception is the Sense A mechanoreceptor is a Sensory receptor that responds to mechanical pressure or distortion Those are non-pain sensing receptors, so the development of nociceptors late in neurogeneis allows for their different sensing capabilities. All embryonic nociceptors express the TrkA nerve growth factor (NGF). However, transcription factors that determine the type of nociceptor remain unclear. ^[3]

Following sensory neurogenesis, differentiation occurs and two different types of nociceptors are formed. They are classified as either peptidergic or nonpeptidergic nociceptors. These two sets of receptors express distinct repertoires of ion channels and receptors. With their specialization, it allows the receptors to innvervate different peripheral and central targets. This differentiation occurs in both perinatal and postnatal periods. The nonpeptidergic nociceptors switch off the TrkA nerve growth factor and begin expressing Ret. Ret is a transmembrane signaling component which allows for the expression of another growth factor—glial cell-derived growth factor (GDNF). This transition is assisted by Runx1 which has proven to be vital in the development of nonpeptidergic nociceptors. On the contrary, the peptidergic nociceptors continue to use TrkA and they express a completely different type of growth factor. Currently there is a lot of research being done to determine more specifically what creates the differences between nociceptors. ^[3]

Types and functions

The peripheral terminal of the mature nociceptor is where the noxious stimuli are detected and transduced into electrical energy. When the electrical energy reaches a threshold value, an action potential is induced and driven towards the CNS. In Neurophysiology, the action potential is a self-regenerating Wave of Electrochemical activity that allows Nerve cells to carry a signal This leads to the train of events that allows for the conscious awareness of pain. The sensory specificity of nociceptors is established by the high threshold only to particular features of stimuli. Only when the high threshold has been reach by either chemical, thermal, or mechanical environments are the nociceptors triggered. Majority of nociceptors are classified by which of the environmental modalities they respond to. Some nociceptors respond to more than one of these modalities and are consequently designated polymodal. Other nociceptors respond to none of these modalities (although they may respond to stimulation under conditions of inflammation) and have thereby earned the more poetic title of sleeping or silent nociceptors.

Nociceptors have two different types of axons. The first are the Aδ fiber axons. A delta fibers, or Aδ fibers are a Type of sensory fiber. They are associated with cold and pressure and as Nociceptors they convey fast Pain information They are myelinated and can allow an action potential to travel at a rate of about 20 meters/second towards the CNS. The other type is the more slowly conducting C fiber axons. Structure and Anatomy Location C fibers are found in the peripheral nerves of the somatic sensory system. These only conduct at speeds of around 2 meters/second. ^[4] This is due to the light or non-myelination of the axon. As a result, pain comes in two phases. The first phase is mediated by the fast-conducting Aδ fibers and the second part due to (Polymodal) C fibers. The pain associated with the Aδ fibers can be associated to an initial extremely sharp pain. The second phase is a more prolonged and slightly less intense feeling of pain as a result from the damage. If there is massive or prolonged input to a C fiber there is progressive build up in the spinal cord dorsal horn. This phenomenon is similar to tetanus in muscles but is called wind-up. If wind up occurs there is a probability of increased sensitivity to pain. ^[5]

Thermal

Thermal nociceptors are activated by noxious heat or cold at various temperatures. There are specific nociceptor transducers that are responsible for how and if the specific nerve ending responds to the thermal stimulus. The first to be discovered was TRPV1, and it has a threshold that coincides with the heat pain temperature of 42°C. Other temperature in the warm-hot range is mediated by more than one TRP channel. Each of these channels express a particular C-terminal domain that corresponds to the warm-hot sensitivity. The interactions between all these channels and how the temperature level is determined to be above the pain threshold are unknown at this time. The cool stimuli are sensed by TRMP8 channels. Its C-terminal domain differs from the heat sensitive TRPs. Although this channel corresponds to cool stimuli, it is still unknown whether it also contributes in the detection of intense cold. An interesting finding related to cold stimuli is that tactile sensibility and motor function deteriorate while pain perception persists.

Mechanical

Mechanical nociceptors respond to excess pressure or mechanical deformation. They also respond to incisions that break the skin surface. The reaction to the stimulus is processed as pain by the cortex, just like chemical and thermal responses. Many times these mechanical nociceptors have polymodal characteristics. So it is possible that some of the transducers for thermal stimuli are the same for mechanical stimuli. The same is true for chemical stimuli, since TRPA1 appears to detect both mechanical and chemical changes.

Chemical

Chemical nociceptors have TRP channels that respond to a wide variety of spices commonly used in cooking. The one that sees the most response and is very widely tested is Capsaicin. Capsaicin /ˌkæpˈseˌɪsɪn/ (8- Methyl - N - Vanillyl -6-nonen Amide) is the active component of Chili peppers Other chemical stimulants are environmental irritants like acrolein, a World War I chemical weapon and a component of cigarette smoke. Acrolein (systematic name 2-propenal) is the simplest unsaturated Aldehyde. World War I (abbreviated WWI; also known as the First World War, the Great War, and the War to End All Chemical warfare involves using the toxic properties of Chemical substances to kill injure or incapacitate an enemy. Besides from these external stimulants, chemical nociceptors have the capacity to detect endogenous ligands, and certain fatty acid amines that arise from changes in internal tissues. Like in thermal nociceptors, TRPV1 can detect chemicals like capsaicin and spider toxins. ^[3]

Sleeping/silent

Although each nociceptor can have a variety of possible threshold levels, some do not respond at all to chemical, thermal or mechanical stimuli unless injury actually has occurred. These are typically referred to as silent or sleeping nociceptors since their response comes only on the onset of inflammation to the surrounding tissue. ^[2]

Pathway

Afferent nociceptive fibers (those that send information to, rather than from the brain) travel back to the spinal cord where they form synapses in its dorsal horn. In the Nervous system, afferent neurons --otherwise known as sensory or receptor Neurons -carry nerve impulses from receptors or sense The spinal cord is a long thin tubular bundle of Nerves that is an extension of the Central nervous system from the brain and is enclosed in and protected The posterior horn ( posterior cornu, dorsal horn, spinal dorsal horn) of the Spinal cord is the dorsal (more towards the back grey matter of This nociceptive fiber (located in the periphery) is a first order neuron. The cells in the dorsal horn are divided into physiologically distinct layers called laminae. The cell is the structural and functional unit of all known living Organisms It is the smallest unit of an organism that is classified as living and is often called Different fiber types form synapses in different layers. Chemical synapses are specialized junctions through which Neurons signal to each other and to non-neuronal cells such as those in Muscles or Glands Aδ fibers form synapses in laminae I and V, C fibers connect with neurons in lamina II, Aβ fibers connect with lamina I, III, & V. ^[2] After reaching the specific lamina within the spinal cord, the first order nociceptive project to second order neurons and cross the midline. The second order neurons then send their information via two pathways to the thalamus: the dorsal column medial-lemniscal system and the anterolateral system. The thalamus (from Greek θάλαμος = room chamber, IPA= /ˈθæləməs/ is a pair and symmetric part of the brain The first is reserved more for regular non-painful sensation, while the lateral is reserved for pain sensation. Upon reaching the thalamus, the information is processed in the ventral posterior nucleus and sent to the cerebral cortex in the brain. The cerebral cortex is a structure within the Brain that plays a key role in Memory, Attention, perceptual Awareness, Thought, As there is an ascending pathway to the brain that initiates the conscious realization of pain, there also is a descending pathway which modulates pain sensory. The brain can request the release of specific hormones or chemicals that can have analgesic effects which can reduce or inhibit pain sensation. Hormones (from Greek ὁρμή - "impetus" are chemicals released by cells that affect cells in other parts of the body area of the brain that can release some of these hormones is the hypothalamus. The hypothalamus links the Nervous system to the Endocrine system via the Pituitary gland (hypophysis ^[6]

This effect of descending inhibition can be shown by electrically stimulating the periaqueductal grey area of the midbrain. Periaqueductal gray (PAG also called the "central gray" is the Midbrain Grey matter that is located around the Cerebral aqueduct within the The periaqueductal grey in turn projects to other areas invovled in pain regulation, such as the nucleus raphe magnus (which also receives similar afferents from the nucleus reticularis paragigantocellularis (NPG). The nucleus raphe magnus, located directly rostral to the Raphe obscurus, is afferently stimulated from axons in the Spinal cord and Cerebellum. In turn the nucleus raphe magnus projects to the substantia gelatinosa region of the dorsal horn and mediates the sensation of spinothalamic inputs. The periaqueductal grey also contains opioid receptors which explains one of the mechanisms by which opioids such as morphine and diacetylmorphine exhibit an analgesic effect. Opioid receptors are a group of G-protein coupled receptors with Opioids as Ligands The Endogenous Opioids are Dynorphins Medical uses Morphine can be used as an analgesic in hospital settings to relieve pain in Myocardial infarction pain in Heroin ( INN: diacetylmorphine, BAN: diamorphine) is a semi-synthetic opioid synthesized from Morphine, a derivative

Sensitivity

Nociceptor neuron sensitivity is modulated by a large variety of mediators in the extracellular space. ^[7] Peripheral sensitization represents a form of functional plasticity of the nociceptor. The nociceptor can change from being simply a noxious stimulus detector to a detector of non-noxious stimuli. The result is that low intensity stimuli from regular activity, initiates a painful sensation. This is commonly known as hyperalgesia. Hyperalgesia is an increased sensitivity to Pain, which may be caused by damage to Nociceptors or Peripheral nerves. Inflammation is one common cause that results in the sensitization of nociceptors. Normally hyperalgesia ceases when inflammation goes down, however, sometimes genetic defects and/or repeated injury can result in allodynia: a completely non-noxious stimulus like light touch causes extreme pain. Allodynia, meaning "other pain" is a Painful response to a usually non-painful stimulus and can be either static or mechanical Allodynia can also be caused when a nociceptor is damaged in the peripheral nerves. This can result in deafferentation, which means the development of different central processes from the surviving afferent nerve. With this situation, surviving dorsal root axons of the nociceptors can make contact with the spinal cord, thus changing the normal input. ^[5]

Nociceptors in non-mammalian animals

Nociception has been documented in non-mammalian animals, including fishes^[8] and a wide range of invertebrates, including leeches^[9], nematode worms^[10], sea slugs^[11], and fruit flies^[12]. Although these neurons may have different pathways and relationships to the central nervous system than mammalian nociceptors, nociceptive neurons in non-mammals often fire in response to similar stimuli as mammals, such as high temperature (40 degrees C or more), low pH, capsaicin, and tissue damage.

Terminology

Due to historical understandings of pain, nociceptors are also called pain receptors. This usage is not consistent with the modern definition of pain as a subjective experience.

See also

• TRPC ion channel
• Piperidine from black pepper

References

© 2009 citizendia.org; parts available under the terms of GNU Free Documentation License, from http://en.wikipedia.org
Dapyx Software network: MP3 Explorer | Ebook Manager | Zenithic