Differential blockade of nerve injury-induced thermal and tactile hypersensitivity by systemically administered brain-penetrating and peripherally restricted local anesthetics

Qingmin Chen, Tamara King, Todd W Vanderah, Michael H. Ossipov, T. Philip Malan, Josephine Lai, Frank Porreca

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Systemic administration of local anesthetics has been shown to transiently reverse thermal and tactile hypersensitivity induced by peripheral nerve injury, effects that have been taken as suggesting direct actions on the peripheral nerves. The present study sought to determine whether a central site of action could contribute to, or account for, the effects of lidocaine on nerve injury-induced thermal and tactile hypersensitivity. Systemic lidocaine and its peripherally restricted analogues, QX-314 or QX-222, effectively reversed thermal hypersensitivity after spinal nerve ligation injury. Nerve injury-induced tactile hypersensitivity, however, was reversed by systemic lidocaine but not QX-314 or QX-222. Microinjection of either lidocaine or QX-314 into the rostral ventromedial medulla fully reversed spinal nerve ligation-induced thermal and tactile hypersensitivity. The data strongly suggest that nerve injury-induced thermal and tactile hypersensitivity are mediated through different mechanisms. In addition, the present study supports a prominent contribution of the central nervous system in the activity of systemically given lidocaine against nerve injury-induced tactile and thermal hypersensitivity. Thus, lidocaine might reverse tactile hypersensitivity mainly through its actions within the central nervous system, whereas its reversal of thermal hypersensitivity might occur through either central or peripheral sites. Perspective Nerve injury-induced neuropathic pain has proved remarkably difficult to treat. Systemic administration of ion channel blockers such as lidocaine has been explored for the management of chronic pain. This work indicates that systemic rather than local administration of lidocaine would be more effective in treating tactile allodynia.

Original languageEnglish (US)
Pages (from-to)281-289
Number of pages9
JournalJournal of Pain
Volume5
Issue number5
DOIs
StatePublished - Jun 2004

Fingerprint

Nerve Block
Touch
Local Anesthetics
Lidocaine
Hypersensitivity
Hot Temperature
Wounds and Injuries
Brain
Spinal Nerves
Ligation
Central Nervous System
Peripheral Nerve Injuries
Hyperalgesia
Microinjections
Neuralgia
Ion Channels
Peripheral Nerves
Chronic Pain

Keywords

  • Lidocaine
  • neuropathic pain
  • QX-222
  • QX-314
  • tactile allodynia
  • thermal hyperalgesia

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Clinical Neurology
  • Neurology
  • Nursing(all)

Cite this

Differential blockade of nerve injury-induced thermal and tactile hypersensitivity by systemically administered brain-penetrating and peripherally restricted local anesthetics. / Chen, Qingmin; King, Tamara; Vanderah, Todd W; Ossipov, Michael H.; Malan, T. Philip; Lai, Josephine; Porreca, Frank.

In: Journal of Pain, Vol. 5, No. 5, 06.2004, p. 281-289.

Research output: Contribution to journalArticle

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