Local anesthetic treatment significantly attenuates acute pain responding but does not prevent the neonatal injury-induced reduction in adult spinal behavioral plasticity.

Abstract

Recent findings indicate that neonatal injury results in decreased spinal plasticity in adult subjects (E. E. Young, K. M. Baumbauer, A. E. Elliot, & R. L. Joynes, 2007). Previous research has shown that acute manipulations of pain processing (i.e., administration of formalin, carrageenan, capsaicin) result in a loss of spinal behavioral plasticity (A. R. Ferguson, E. D. Crown, & J. W. Grau, 2006). Moreover, neonatal injury results in a lasting reduction in adult spinally mediated plasticity resembling the deficit seen following acute manipulations in adults (E. E. Young et al., 2007). The present study was designed to determine whether the effects of neonatal injury could be prevented by lidocaine administration during the initial healing period. Subjects (injured or uninjured) received lidocaine or saline on 1 of 4 administration schedules (preinjury only, postinjury only, for 24 hr postsurgery, or for 72 hr postsurgery). Results demonstrated that lidocaine administration did not prevent the hypersensitivity and reduced spinal plasticity associated with neonatal injury. This suggests that (a) the mechanisms underlying neonatal injury are independent of peripheral input in the initial healing period and (b) lidocaine is ineffective at preventing long-term spinal plasticity changes following neonatal injury.

Timing in the absence of supraspinal input III: Regularly spaced cutaneous stimulation prevents and reverses the spinal learning deficit produced by peripheral inflammation.

“…Supporting this, we have shown that uncontrollable shock enhances mechanical reactivity (Ferguson et al, 2006) and that manipulations which induce central sensitization, such as peripheral inflammation (e.g. from capsaicin administration) or tissue damage, also inhibit instrumental learning (Hook et al, 2008; Young, Baumbauer, Hillyer, & Joynes, 2007; Young et al, 2008). Further, just as controllable stimulation can both prevent and reverse the learning deficit induced by uncontrollable shock, it has a protective/restorative effect on the inflammation-induced allodynia and learning impairment (Hook et al, 2008).…”

Group I Metabotropic Glutamate Receptors Control Metaplasticity of Spinal Cord Learning through a Protein Kinase C-Dependent Mechanism

“…This supports other work linking metaplastic inhibition of spinal learning with nociceptive plasticity. Inhibition of spinal learning can be induced by incision injury or intradermal carrageenan and uncontrollable shock produces a tactile hyper-reactivity (Ferguson et al, 2006; Young et al, 2007). In addition, inhibition of spinal learning involves receptor systems known to modulate pain, including neurokinin (Baumbauer et al, 2007b), kappa opioid (Joynes and Grau, 2004; Washburn et al, 2008), GABA A (Ferguson et al, 2003), and 5-HT receptors (Crown and Grau, 2005).…”

Design and Assessment of a Potent Sodium Channel Blocking Derivative of Mexiletine for Minimizing Experimental Neuropathic Pain in Several Rat Models

“…channel blocking activity, with previous studies having shown other Na ? channel blockers, such as tetrodotoxin and lidocaine derivatives, to inhibit nerve signal transduction and neurological pain [28,29]. Indeed, mexiletinetreatment has been demonstrated to afford anti-allodynic effects to neuropathic pain in spinally injured rats [30].…”

“…Both drugs were very effective in blocking licking in the 2-5 min period after formalin injection (phase 1) in that six out of eight rats did not lick whereas six out of eight rats injected only with formalin licked with a mean of three licks in the 3 min period. In phase 2 (25-60 min), licks were counted at an early period (25)(26)(27)(28)(29)(30) and a late period (55-60) and the data pooled. The drugs reduced the number of licks although not as effectively as in phase 1 (Fig.…”