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(NAS Colloquium) The Neurobiology of Pain (1999) / Chapter Skim
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A Comparison of the Potential Role of the Tetrodotoxin-insensitive Sodium Channels, PN3/SNS and NaN/SNS2, in Rat Models of Chronic Pain
Pages 7640-7644

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From page 7640...
... Spontaneous and/or evoked hyperexcitability of the peripheral nerve after injury is considered to be a principal feature of the underlying pathophysiology associated with many chronic, in particular neuropathic, pain syndromes (1, 2~. A prominent molecular basis for this abnormal, repetitive firing of injured primary afferents is an accumulation and increased membrane density of sodium channels at focal sites of injury (3, 4~.
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From page 7641...
... Such observations provide additional support for the involvement of uninjured primary afferents in adjacent segments of the sciatic nerve in mediating certain types of neuropathic pain behaviors (30~. The reasons for increased PN3 expression in large diameter cells in the non-injured L4 DRG after SNL and decreases in PN3 expression in cell bodies of the injured L5/L6 DRG are unclear but may reflect the differential availability of factors such as nerve growth factor, which is known to be released from peripheral tissues and to be retrogradely transported to the ganglion, where it regulates mRNA expression of PN3 (31)
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From page 7642...
... Cessation of the antisense ODN treatment at any time after the SNL injury results in the reoccurrence of tactile allodynia and thermal hyperalgesia within 48 hr. demonstrating the reversibility of the ODN effect.
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From page 7643...
... This view is borne out by noting that inhibition of PN3 protein expression by the antisense ODN does not affect normal noxious and non-noxious sensory thresholds on the contralateral side to the nerve injury and fails to affect the allodynia and hyperalgesia seen after carrageenan, an acute inflammation with a time-course that would not likely be associated with new channel protein synthesis. However, prevention of protein synthesis by pretreatment with antisense ODN before, or during, chronic injuries, such as SNL or CFA, results in a complete inhibition of the development of the behavioral consequences of the injury.
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From page 7644...
... The lack of any overt, particularly central nervous system, adverse events with the antisense ODN was consistent with the previously described discrete localization of the channel to sensory nerve fibers with an absence of staining in the central nervous system and cardiac tissue (20~. It also reaffirms the potential that a selective inhibitor of PN3 may be clinically analgesic, providing not only an improved therapeutic window over existing therapies, but offering relief from neuropathic pain that is normally resistant to current therapies.
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Key Terms

  • sodium channel
  • diameter cells
  • thermal hyperalgesia
  • antisense odn
  • tactile allodynia

  • tissue injury
  • sodium channels
  • drg cells
  • nerve injury
  • snl animals

  • snl injury
  • naive animals
  • spinal nerve
  • neuropathic pain
  • repetitive firing

  • biophysical properties
  • pathophysiological role
  • central nervous
  • protein synthesis
  • similar pattern

  • antibody labeling
  • nerve ligation
  • cells expressing
  • paw withdrawal
  • protein expression

  • channel protein
  • behavioral consequences
  • recently cloned
  • treated controls
  • behavioral thermal


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