Sensitization

Sensitization is a non-associative learning process in which repeated administration of a stimulus results in the progressive amplification of a response.[1] Sensitization often is characterized by an enhancement of response to a whole class of stimuli in addition to the one that is repeated. For example, repetition of a painful stimulus may make one more responsive to a loud noise.

This article is about the concept in psychology. For the concept in immunology, see Sensitization (immunology). For Central sensitization (physiologic pathology), see Central sensitization.

History

Eric Kandel was one of the first to study the neural basis of sensitization, conducting experiments in the 1960s and 1970s on the gill withdrawal reflex of the seaslug Aplysia. Kandel and his colleagues first habituated the reflex, weakening the response by repeatedly touching the animal's siphon. They then paired noxious electrical stimulus to the tail with a touch to the siphon, causing the gill withdrawal response to reappear. After this sensitization, a light touch to the siphon alone produced a strong gill withdrawal response, and this sensitization effect lasted for several days. (After Squire and Kandel, 1999[2]). In 2000, Eric Kandel was awarded the Nobel Prize in Physiology or Medicine for his research in neuronal learning processes.

Neural substrates
Addiction and dependence glossary[3][4][5]
  • addiction – a biopsychosocial disorder characterized by persistent use of drugs (including alcohol) despite substantial harm and adverse consequences
  • addictive drug – psychoactive substances that with repeated use are associated with significantly higher rates of substance use disorders, due in large part to the drug's effect on brain reward systems
  • dependence – an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake)
  • drug sensitization or reverse tolerance – the escalating effect of a drug resulting from repeated administration at a given dose
  • drug withdrawal – symptoms that occur upon cessation of repeated drug use
  • physical dependence – dependence that involves persistent physical–somatic withdrawal symptoms (e.g., fatigue and delirium tremens)
  • psychological dependence – dependence socially seen as being extremely mild compared to physical dependence (e.g., With enough willpower it could be overcome)
  • reinforcing stimuli – stimuli that increase the probability of repeating behaviors paired with them
  • rewarding stimuli – stimuli that the brain interprets as intrinsically positive and desirable or as something to approach
  • sensitization – an amplified response to a stimulus resulting from repeated exposure to it
  • substance use disorder – a condition in which the use of substances leads to clinically and functionally significant impairment or distress
  • tolerance – the diminishing effect of a drug resulting from repeated administration at a given dose

The neural basis of behavioral sensitization is often not known, but it typically seems to result from a cellular receptor becoming more likely to respond to a stimulus. Several examples of neural sensitization include:

  • Electrical or chemical stimulation of the rat hippocampus causes strengthening of synaptic signals, a process known as long-term potentiation or LTP.[6] LTP of AMPA receptors is a potential mechanism underlying memory and learning in the brain.
  • In "kindling", repeated stimulation of hippocampal or amygdaloid neurons in the limbic system eventually leads to seizures in laboratory animals. After sensitization, very little stimulation may be required to produce seizures. Thus, kindling has been suggested as a model for temporal lobe epilepsy in humans, where stimulation of a repetitive type (flickering lights for instance) can cause epileptic seizures.[7] Often, people suffering from temporal lobe epilepsy report symptoms of negative effects such as anxiety and depression that might result from limbic dysfunction.[8]
  • In "central sensitization", nociceptive neurons in the dorsal horns of the spinal cord become sensitized by peripheral tissue damage or inflammation.[9] This type of sensitization has been suggested as a possible causal mechanism for chronic pain conditions. The changes of central sensitization occur after repeated trials to pain. Research from animals has consistently shown that when a trial is repeatedly exposed to a painful stimulus, the animal’s pain threshold will change and result in a stronger pain response. Researchers believe that there are parallels that can be drawn between these animal trials and persistent pain in people. For example, after a back surgery that removed a herniated disc from causing a pinched nerve, the patient may still continue to feel pain. Also, newborns who are circumcised without anesthesia have shown tendencies to react more greatly to future injections, vaccinations, and other similar procedures. The responses of these children are an increase in crying and a greater hemodynamic response (tachycardia and tachypnea).[10]
  • Drug sensitization occurs in drug addiction, and is defined as an increased effect of drug following repeated doses (the opposite of drug tolerance). Such sensitization involves changes in brain mesolimbic dopamine transmission, as well as a protein inside mesolimbic neurons called delta FosB. An associative process may contribute to addiction, for environmental stimuli associated with drug taking may increase craving. This process may increase the risk for relapse in addicts attempting to quit.[11]

Cross-sensitization

Cross-sensitization is a phenomenon in which sensitization to a stimulus is generalized to a related stimulus, resulting in the amplification of a particular response to both the original stimulus and the related stimulus.[12][13] For example, cross-sensitization to the neural and behavioral effects of addictive drugs are well characterized, such as sensitization to the locomotor response of a stimulant resulting in cross-sensitization to the motor-activating effects of other stimulants. Similarly, reward sensitization to a particular addictive drug often results in reward cross-sensitization, which entails sensitization to the rewarding property of other addictive drugs in the same drug class or even certain natural rewards.

In animals, cross-sensitization has been established between the consumption of many different types of drugs of abuse – in line with the gateway drug theory – and also between sugar consumption and the self-administration of drugs of abuse.[14]

As a causal factor in pathology

Sensitization has been implied as a causal or maintaining mechanism in a wide range of apparently unrelated pathologies including addiction, allergies, asthma, overactive bladder[15] and some medically unexplained syndromes such as fibromyalgia and multiple chemical sensitivity. Sensitization may also contribute to psychological disorders such as post-traumatic stress disorder, panic anxiety and mood disorders.[16][17][18]

See also

References
  1. Shettleworth, S. J. (2010). Cognition, Evolution and Behavior (2nd ed.). New York: Oxford.
  2. Squire LR, Kandel ER (1999). Memory: From Mind to Molecules. New York: Scientific American Library; New York: W.H. Freeman. ISBN 0-7167-6037-1.
  3. Nestler EJ (December 2013). "Cellular basis of memory for addiction". Dialogues in Clinical Neuroscience. 15 (4): 431–443. PMC 3898681. PMID 24459410. Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. ... A large body of literature has demonstrated that such ΔFosB induction in D1-type [nucleus accumbens] neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement ... Another ΔFosB target is cFos: as ΔFosB accumulates with repeated drug exposure it represses c-Fos and contributes to the molecular switch whereby ΔFosB is selectively induced in the chronic drug-treated state.41 ... Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict.
  4. Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and Addictive Disorders". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 364–375. ISBN 9780071481274.
  5. Volkow ND, Koob GF, McLellan AT (January 2016). "Neurobiologic Advances from the Brain Disease Model of Addiction". New England Journal of Medicine. 374 (4): 363–371. doi:10.1056/NEJMra1511480. PMC 6135257. PMID 26816013. Substance-use disorder: A diagnostic term in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) referring to recurrent use of alcohol or other drugs that causes clinically and functionally significant impairment, such as health problems, disability, and failure to meet major responsibilities at work, school, or home. Depending on the level of severity, this disorder is classified as mild, moderate, or severe.
    Addiction: A term used to indicate the most severe, chronic stage of substance-use disorder, in which there is a substantial loss of self-control, as indicated by compulsive drug taking despite the desire to stop taking the drug. In the DSM-5, the term addiction is synonymous with the classification of severe substance-use disorder.
  6. Collingridge, Graham L.; Isaac, John T. R.; Wang, Yu Tian (2004). "Receptor trafficking and synaptic plasticity". Nature Reviews Neuroscience. 5 (12): 952–962. doi:10.1038/nrn1556. PMID 15550950. S2CID 15918122.
  7. Morimoto, Kiyoshi; Fahnestock, Margaret; Racine, Ronald J. (2004). "Kindling and status epilepticus models of epilepsy: Rewiring the brain". Progress in Neurobiology. 73 (1): 1–60. doi:10.1016/j.pneurobio.2004.03.009. PMID 15193778. S2CID 36849482.
  8. Teicher, M. H.; Glod, C. A.; Surrey, J.; Swett Jr, C. (1993). "Early childhood abuse and limbic system ratings in adult psychiatric outpatients". The Journal of Neuropsychiatry and Clinical Neurosciences. 5 (3): 301–6. doi:10.1176/jnp.5.3.301. PMID 8369640.
  9. Ji, R. R.; Kohno, T.; Moore, K. A.; Woolf, C. J. (2003). "Central sensitization and LTP: Do pain and memory share similar mechanisms?". Trends in Neurosciences. 26 (12): 696–705. doi:10.1016/j.tins.2003.09.017. PMID 14624855. S2CID 14214986.
  10. Gudin, J. (2004). "Expanding Our Understanding of Central Sensitization". Medscape Neurobiology. 6 (1).
  11. Robinson, T. E.; Berridge, K. C. (1993). "The neural basis of drug craving: An incentive-sensitization theory of addiction". Brain Research. Brain Research Reviews. 18 (3): 247–91. doi:10.1016/0165-0173(93)90013-p. hdl:2027.42/30601. PMID 8401595. S2CID 13471436.
  12. Brumovsky PR, Gebhart GF (February 2010). "Visceral organ cross-sensitization – an integrated perspective". Autonomic Neuroscience: Basic & Clinical. 153 (1–2): 106–15. doi:10.1016/j.autneu.2009.07.006. PMC 2818077. PMID 19679518.
  13. Malykhina AP, Wyndaele JJ, Andersson KE, De Wachter S, Dmochowski RR (March 2012). "Do the urinary bladder and large bowel interact, in sickness or in health? ICI-RS 2011". Neurourology and Urodynamics. 31 (3): 352–8. doi:10.1002/nau.21228. PMC 3309116. PMID 22378593.
  14. Avena NM, Rada P, Hoebel BG (2008). "Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake". Neuroscience and Biobehavioral Reviews. 32 (1): 20–39. doi:10.1016/j.neubiorev.2007.04.019. PMC 2235907. PMID 17617461.
  15. Reynolds WS, Dmochowski R, Wein A, Bruehl S (August 2016). "Does central sensitization help explain idiopathic overactive bladder?". Nature Reviews. Urology. 13 (8): 481–91. doi:10.1038/nrurol.2016.95. PMC 4969200. PMID 27245505.
  16. Rosen, Jeffrey B.; Schulkin, Jay (1998). "From normal fear to pathological anxiety". Psychological Review. 105 (2): 325–350. doi:10.1037/0033-295X.105.2.325. PMID 9577241.
  17. Antelman, Seymour M. (1988). "Time-dependent sensitization as the cornerstone for a new approach to pharmacotherapy: Drugs as foreign/Stressful stimuli". Drug Development Research. 14: 1–30. doi:10.1002/ddr.430140102. S2CID 144698255.
  18. Post, R. M. (1992). "Transduction of psychosocial stress into the neurobiology of recurrent affective disorder". The American Journal of Psychiatry. 149 (8): 999–1010. doi:10.1176/ajp.149.8.999. PMID 1353322.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.