Mechanical allodynia

Abstract

Mechanical allodynia (other pain) is a painful sensation caused by innocuous stimuli like light touch. Unlike inflammatory hyperalgesia that has a protective role, allodynia has no obvious biological utility. Allodynia is associated with nerve damage in conditions such as diabetes, and is likely to become an increasing clinical problem. Unfortunately, the mechanistic basis of this enhanced sensitivity is incompletely understood. In this review, we describe evidence for the involvement of candidate mechanosensitive channels such as Piezo2 and their role in allodynia, as well as the peripheral and central nervous system mechanisms that have also been implicated in this form of pain. Specific treatments that block allodynia could be very useful if the cell and molecular basis of the condition could be determined. There are many potential mechanisms underlying this condition ranging from alterations in mechanotransduction and sensory neuron excitability to the actions of inflammatory mediators and wiring changes in the CNS. As with other pain conditions, it is likely that the range of redundant mechanisms that cause allodynia will make therapeutic intervention problematic.

Identification of Spinal Circuits Transmitting and Gating Mechanical Pain

“…Thus, pain is encoded through a hybrid mechanism that combines Perl’s specificity and Wall’s pattern theories, a mechanism recently referred to as the population coding theory (Ma, 2010, 2012; Prescott et al, 2014). Clinically, mechanical pain treatment represents a big challenge (Lolignier et al, 2014). Our study suggests that drugs targeted at reducing excitatory output from SOM neurons or enhancing inhibitory output from Dyn neurons could be ideally used to attenuate mechanical allodynia, without affecting the senses of temperature and touch that are vital for daily life.…”

Piezo Proteins: Regulators of Mechanosensation and Other Cellular Processes

“…In many cases, it appears to involve aberrant sensitivity to mechanical force at the level of cutaneous mechanoreceptors or primary afferent neurons. Mechanical allodynia, associated with several neuropathies, is the disease where normally innocuous stimuli are perceived as excruciatingly painful (52). No specific treatments are available beyond palliative measures.…”

Kinetic disruption of lipid rafts is a mechanosensor for phospholipase D

“…It is the underlying mechanism for both touch and hearing and is known to have roles in cancer, allodynia heart and vascular disease12. The plasma membrane is thought to couple force directly with effector molecules such as mechanosensitive ion channels345 and organize mechanosensitive proteins including focal adhesion proteins6.…”