Friday, April 17, 2009

Itching Phantoms

Is The Itch an epidemic?

• The Itch is the most frequent complaint from dermatologists’ patients (Gieler & Walter 2008).
• Approximately 8 to 10% of the world’s human population suffers from chronic itching, medically known as neurodermatitis (Gieler & Walter 2008).
• In 2006 approximately 300 million people suffered from scabies, a skin disorder in which biting mites cause irritation and itchiness (The Lancet Infectious Diseases as cited in Miller 2007).
• Also in 2006, a study found that 42% of nearly 19,000 kidney-dialyses patients, representing 12 countries, reported a moderate to severe itch (Nephrology Dialysis Transplantation as cited in Miller 2007).
• In August 2007 an estimated 31.6 million Americans experienced skin itchiness induced by eczema (Dermatitis as cited in Miller 2007).
• The Fourth International Workshop for the Study of the Itch took place in San Francisco in April 2007.

The Itch as seen in the brain.

Scientists believe itching evolved as a survival tactic to ward off potential hazards such as insects by drawing attention to the vulnerable area. As Atul Gawande (2008) references in his article, the definition of The Itch, termed by physicians as pruritus, has not been replaced since 1660 when the German physician Samuel Hafenreffer referred to it as, “An unpleasant sensation that provokes the desire to scratch.” This definition addresses the two main components of pruritus: the negative sensation itself and our bodies’ instinctive treatment for it- scratching. Leknes et al. (2006) found that two types of itching, histamine and allergen-induced, both stimulated limbic and ventral prefrontal activation. The researchers go on to explain that the activation of both regions correlates with the individual’s desire to itch. In addition, the two areas are associated with motivation processing. Scratching offers an immediate reward. Although an individual may understand intellectually that scratching is not remedial in the long term, the brain can override this logic because it focuses on immediate rather than future rewards.

In terms of M.’s case, and any other patient suffering from chronic itching, the extensive circuitry involved in The Itch can be extremely problematic. Treatment must mitigate the sensation but also our motor response.

A study done at the Bender Institute of Neuroimaging at the University of Giessen in Germany used fMRI to show that histamine-induced itching did not activate the sensorimotor cortex, but rather areas of the frontal lobe, left temporal lobe and the left hemisphere of the cerebellum (Gieler & Walter 2008). Furthermore, research done by Handwerker evidences the stimulation of the amygdala and Hideki Mochizuki in Japan documented the activation of the cingulum, “a switching center that processes emotions, and the insula, an area also associated with emotion and disgust, both fire during itching-but not during pain” (Gieler & Walter 2008). The cingulum is a fiber tract of white matter, above the corpus collasum. In patients with neurodermatitis scratching does not inhibit the cingulum, thus The Itch is exacerbated by emotions (Gieler & Walter 2008).

The Itch versus Pain.

Historically, pruritus was considered as a lesser form of pain. This is known as the intensity theory (Gieler & Walter 2008). Both sensations travel from the periphery to the spinal cord along C-fibers. Less stimulation in C-fibers was believed to produce itchiness. If stimulation were increased the itchiness would turn into pain. As Gawande (2008) explains, The Itch is not a subset of pain, but rather an entirely separate sensation. Even so, it is interesting that because there are connections between itch and pain pathways, they influence each other (Gieler & Walter 2008); pain tends to quell itching, and painkillers tend to produce itchiness. (Miller 2007). In addition, scratching and rubbing offer momentary relief because they trigger pain and touch receptors, subduing pruritus (Gieler & Walter 2008). In 1997, Martin Schmelz, now working at the University of Manheim in Germany, declared that his research team had found C-fibers that did not react to painful heat or pinching, but was stimulated when histamine was injected into the skin of healthy individuals (Miller 2007). In addition, H. Erik Torebjork from Sweden reported that nerve fibers associated with itching are not myelinated. Thus, blocking electrical stimulation along myelinated nerve fibers will not stop the itching sensation (Perkins 1997).

Relieving The Itch.

Research for treatment for pruritus and neurodermatitis is ongoing. One promising drug is a blocker for gastrin-releasing peptide receptors (GRPR). A study done with mice shows the absence of the gene for GRPR results in mitigated itching. In addition, calming techniques such as autogenic training “(in which patients repeat a set of visualizations) and Jacobson’s progressive muscle relaxation (in which patients relax muscles to relieve tension), have proved effective in supplementing medical treatment” (Gieler & Walter 2008). Such treatments are logical knowing that stress is the second most prominent catalyst for itching. Allergens are first. Dalgard et al. (2006) found from a questionnaire that the 27% of subjects that reported itching were younger, generally female, non-Norwegian, were of lower-income, more distressed and undergone more negative life events and finally had poorer social support. In 1949 a study done by Dr. Cormia proposed that patients experiencing localized itching were suffering from family resentment. Electroshock therapy was suggested as treatment (Science 1949).

Following the experimental lecture, “Itching- what’s behind it?” Niemeier et al. (1999) surmises that itching can be alleviated by verbal and visual stimulation. The first half of the lecture featured “itchy” topics—pictures of fleas, mites, scratch marks on the skin, allergic reactions etc.—while the second exhibited more soothing topics—pictures of baby skin, soft down, bathers, mother with child in her arms etc. Video documentation shows more scratching, and by logical deduction increased itchiness, amongst audience members in the first half of the lecture.

This leads to the discussion of contagious itching being a product of mirror neurons, similar to yawning.

The majority of the research focuses on localizing pruritus, but what if, like in M.’s case, this proves impossible? What if, as Anne Louise Oaklander believed, The Itch had migrated from its proper nerve fibers and established a new loop? What if M.’s brain circuitry had gone haywire? Indeed our brain’s circuitry can go haywire very easily. Gawande (2008) mentions phantom limb; coinciding with phantom limbs is the transformation of somatotopic maps, or as Ramachandran (1998) refers to as “the remapping hypothesis.” and subsequently the projection of sensations to phantom limbs. For example, Ramachandran (1998) found in eight out of eighteen patients, tactile stimulation to the face results in stimulation of the phantom arm.

Ramachandran (1998) hypothesizes that the reworking of neuronal circuits does not entail creating new synaptic connections but rather revealing pre-existing ones. If this is indeed the case, the human brain is setup for remapping. To a certain extent, treatment for a circuit that goes awry is an attempt to mitigate the human brain’s innate plasticity.

Looking at phantoms.
..but first a little experiment.

Ramachandran & Rogers-Ramachandran (1996) explains that phantom limbs are the result of contradictory feedback; specifically, the motor intention to move a limb, is not reinforced by sensory, proprioceptive information. In normal individuals, the frontal lobe, controlling motor actions, communicates (sometimes via the cerebellum) with the parietal lobe. With each motor action, sensory information is attached. In phantom limbs that are rigid, to the point of paralysis, the brain has learned incorrectly that the limb is unable to move. This is where mirror therapy applies. Ramachandran & Rogers-Ramachandran (1996) constructed a virtual reality box, in which the patient perceives the phantom limb moving in the mirror, but in reality they are looking at the reflection of their existing limb. The patient is tricking his brain into receiving false proprioceptive information. With repeated mirror therapy patients are able to unclench fists, relieving pain, and in some cases the phantom limb has vanished.

Similarly, mirror therapy has been tried on patients with complex regional pain syndrome (CRPS). CRPS is similar to phantom limb pain in the sensations it induces- burning, cramping and mislocalized (McCabe et al. 2002). The “phantom” pain may exceed the original pain resulting from trauma, etc. McCabe et al. (2002) argues that similar to phantom limbs, CRPS results from incongruent feedback. In other words, the connection between sensory information and visual confirmation is disrupted. In early CRPS cases the mirror exercises was found to have analgesic effect, however, the mirror did not benefit those with chronic CRPS (McCabe et al. 2002).

Although the virtual reality box has proved affective, Murray et al. (2006) explains the box’s limitations: a narrow spatial dimension and the requirement that the patient only focus on the reflection and ignore the intact limb. He and is colleagues propose “Immersive Virtual Reality,” (IVR). Using a head-mounted display, patients visualize a virtual reality in which their intact limb is superimposed as their phantom limb. The research is in its initial stages but is promising. The researchers’ main concern is the argument that the IVR is a distraction versus a pain mitigator. Patients are required to complete four motor tasks that occupy their attention, distracting them from the pain.

Can mirrors combat The Itch? And further speculations.

At the end of Gawande’s (2008) article he mentions a conversation he has with Ramachandran, in which the neuroscientists suggests mirror therapy for M. There are obvious similarities with pruritus and pain. McCabe et al. (2002) explains, “The classical picture of a pain mechanism as a single hard-wired, dedicated pathway is no longer widely held. Instead, converging evidence from physiological and functional imaging studies suggests a much more diffuse and plastic system, involving the cord, brainstem, thalamus and cortex. In addition, psychological statues such as attention, anticipation and preparation for action may be inherent, essential components modulating the experience of pain.” Pain could be substituted with itch in the above quotation. In phantom limb patients, the brain learns the fixed position of the limb. In CRPS, the brain learns the pain, because it is not finding any relief. What if The Itch is learned as well? If the sensorimotor cortex is not activated at all, as found with histamine-induced itching, this can be even more problematic.

Referring back to M.’s case, the area of her scalp that itched was indeed numb. The specific nerves responsible for the Itch had been killed. However, with no relief (such as scratching) the brain eventually learns that that area of the scalp itches and will persist to itch. M. has yet to try mirror therapy, according to the most recent updates on her case. A couple self-prescribed mirror therapy to help with the husband’s Anesthesia Dolorosa, after reading Gawande’s (2008) article. Anesthesia is a complication from neurosurgery in which facial sensation is reduced to pain ( 2006). The husband was given Neurontin, which alleviated some of the pain from Trigeminal Neuralgia, contracted in 1997. However it had a dual-depressant affect, which had to be counteracted with stimulants such as caffeine, methylphenidate, (Ritalin) and Dexedrine. The husband developed a tolerance and subsequent addiction to the stimulants, as well as cardiac problems. He had to stop using any of the medications, including Neurontin, however, the pain was too severe. The couple decided to try mirror therapy at home and found it was extremely successful. The wife considers it a miracle.

At the present time research is being done to locate the specific modalities of pruritus, however, it seems that The Itch is part of a much larger conceptual issue; the brain is adversely susceptible to its on plasticity. A virtual reality, whether it is using a mirror or a computer, must counteract the reality that exists in our brain, separate to the external world, and idiosyncratic to each individual.


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