Enhancement of experimental pruritus and mechanically evoked dysesthesiae with local anesthesia

Abstract

Pain reduces itch-a commonly known effect of scratching the skin. Experimentally produced itch from histamine is sometimes accompanied by secondary sensations of pain. The present study investigated the effects of eliminating this pain, by means of a local anesthetic, on the itch and the enhanced mechanically evoked itch and pain that occur after an intradermal injection of histamine. In ten human subjects, the volar forearm was injected with either 20 microl of 2% chloroprocaine (experimental arm), or 20 microl of saline (control arm). Histamine 10 microl was injected into each bleb, and the resulting magnitude of itch estimated. The borders of three cutaneous areas were mapped within which mechanical stimulation of the skin surrounding the bleb elicited abnormal sensations (dysesthesiae): alloknesis, defined as itch evoked by innocuous stroking, and hyperalgesia and hyperknesis, characterized, respectively, by enhanced pain and enhanced itch evoked by pricking the skin with a fine tipped filament. The magnitude and duration of itch were significantly greater and the areas of dysesthesia significantly larger for the experimental than for the control arm. It is hypothesized that there exist two classes of histamine-sensitive primary afferent neurons. One class is "pruritic", and mediates itch whereas the other is "antipruritic", and evokes a centrally mediated reduction in histamine-evoked itch and dysesthesiae. It is further suggested that the anesthetic blocked the discharges of the antipruritic afferents, preventing the central inhibition from occurring and thereby unmasking the effects of the pruritic afferents.

Labeled lines meet and talk: population coding of somatic sensations

“…Second, pruriceptors can respond to an allogeneic stimulus, but activation of a larger number of pain-specific fibers can dominantly mask itch (16,86). Indeed, an antagonistic relationship between pain and itch has long been recognized (11,(88)(89)(90)(91). Over 80 years ago, Lewis found that itch evoked by histamine injection can be suppressed by electric stimuli (88).…”

“…Mechanistically, scratching, a painful stimulus, can directly silence the firing of histamine-sensitive neurons in the spinal cord (91). Conversely, an inhibition of pain can enhance histamine-induced itch (90), and itch is a common side effect of analgesic treatment with opioids (11).…”

Cowhage-Evoked Itch Is Mediated by a Novel Cysteine Protease: A Ligand of Protease-Activated Receptors

“…Although most experimental studies of itch use histamine as the pruritic stimulus (Simone et al, 1987;Schmelz et al, 1997;Atanassoff et al, 1999), clinical pruritus is not typically mediated by histamine (Klein and Clark, 1999;Steinhoff et al, 2003). Therefore, the identification of compounds that elicit a strong histamine-independent itch would provide a tool with which to search for novel itch receptors and endogenous ligands.…”

Intracisternal, But Not Intrathecal, Injection of Naloxone Inhibits Cutaneous Itch-Related Response in Mice

“…An intradermal injection of histamine induces hyperalgesia (enhanced prickling pain) and hyperknesis (enhanced pricking-evoked itch), and intradermal pretreatment with the local anesthetic chloroprocaine produces the inhibition of pain and the enhancement of itch. 11) In contrast, itch sensation is generally reduced by pain produced by scratching. Therefore, it was suggested that itch produced by intrathecal and epidural injection of mu-opioid receptor agonists in humans is due to the inhibition of pain input by opioids in the dorsal horn.…”