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Spinal gap junctions: potential involvement in pain facilitation.
J Pain. 2004 Sep; 5(7):392-405.JP

Abstract

Glia are now recognized as important contributors in pathological pain creation and maintenance. Spinal cord glia exhibit extensive gap junctional connectivity, raising the possibility that glia are involved in the contralateral spread of excitation resulting in mirror image pain. In the present experiments, the gap junction decoupler carbenoxolone was administered intrathecally after induction of neuropathic pain in response to sciatic nerve inflammation (sciatic inflammatory neuropathy) or partial nerve injury (chronic constriction injury). In both neuropathic pain models, a low dose of carbenoxolone reversed mirror image mechanical allodynia, while leaving ipsilateral mechanical allodynia unaffected. Ipsilateral thermal hyperalgesia was briefly attenuated. Critically, blockade of mechanical allodynia and thermal hyperalgesia was not observed in response to intrathecal glycyrrhizic acid, a compound similar to carbenoxolone in all respects but it does not decouple gap junctions. Thus, blockade of mechanical allodynia and thermal hyperalgesia by carbenoxolone does appear to reflect an effect on gap junctions. Examination of carbenoxolone's effects on intrathecal human immunodeficiency virus type 1 gp120 showed that blockade of pain facilitation might result, at least in part, via suppression of interleukin-1 and, in turn, interleukin-6. These data provide the first suggestion that spread of excitation via gap junctions might contribute importantly to inflammatory and traumatic neuropathic pain.

PERSPECTIVE

The current studies provide evidence for involvement of gap junctions in spinal cord pain facilitation. Intrathecal carbenoxolone, a gap junction decoupler, reversed neuropathy-induced mirror image pain and intrathecal gp120-induced allodynia. In addition, it decreased gp120-induced proinflammatory cytokines. This suggests gap junction activation might lead to proinflammatory cytokine release by distantly activated glia.

Authors+Show Affiliations

Department of Psychology & The Center for Neuroscience, University of Colorado at Boulder, Boulder, Colorado 90309-0345, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15501197

Citation

Spataro, Leah E., et al. "Spinal Gap Junctions: Potential Involvement in Pain Facilitation." The Journal of Pain, vol. 5, no. 7, 2004, pp. 392-405.
Spataro LE, Sloane EM, Milligan ED, et al. Spinal gap junctions: potential involvement in pain facilitation. J Pain. 2004;5(7):392-405.
Spataro, L. E., Sloane, E. M., Milligan, E. D., Wieseler-Frank, J., Schoeniger, D., Jekich, B. M., Barrientos, R. M., Maier, S. F., & Watkins, L. R. (2004). Spinal gap junctions: potential involvement in pain facilitation. The Journal of Pain, 5(7), 392-405.
Spataro LE, et al. Spinal Gap Junctions: Potential Involvement in Pain Facilitation. J Pain. 2004;5(7):392-405. PubMed PMID: 15501197.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spinal gap junctions: potential involvement in pain facilitation. AU - Spataro,Leah E, AU - Sloane,Evan M, AU - Milligan,Erin D, AU - Wieseler-Frank,Julie, AU - Schoeniger,Diana, AU - Jekich,Brian M, AU - Barrientos,Ruth M, AU - Maier,Steven F, AU - Watkins,Linda R, PY - 2004/05/07/received PY - 2004/06/23/revised PY - 2004/06/29/accepted PY - 2004/10/27/pubmed PY - 2004/12/23/medline PY - 2004/10/27/entrez SP - 392 EP - 405 JF - The journal of pain JO - J Pain VL - 5 IS - 7 N2 - UNLABELLED: Glia are now recognized as important contributors in pathological pain creation and maintenance. Spinal cord glia exhibit extensive gap junctional connectivity, raising the possibility that glia are involved in the contralateral spread of excitation resulting in mirror image pain. In the present experiments, the gap junction decoupler carbenoxolone was administered intrathecally after induction of neuropathic pain in response to sciatic nerve inflammation (sciatic inflammatory neuropathy) or partial nerve injury (chronic constriction injury). In both neuropathic pain models, a low dose of carbenoxolone reversed mirror image mechanical allodynia, while leaving ipsilateral mechanical allodynia unaffected. Ipsilateral thermal hyperalgesia was briefly attenuated. Critically, blockade of mechanical allodynia and thermal hyperalgesia was not observed in response to intrathecal glycyrrhizic acid, a compound similar to carbenoxolone in all respects but it does not decouple gap junctions. Thus, blockade of mechanical allodynia and thermal hyperalgesia by carbenoxolone does appear to reflect an effect on gap junctions. Examination of carbenoxolone's effects on intrathecal human immunodeficiency virus type 1 gp120 showed that blockade of pain facilitation might result, at least in part, via suppression of interleukin-1 and, in turn, interleukin-6. These data provide the first suggestion that spread of excitation via gap junctions might contribute importantly to inflammatory and traumatic neuropathic pain. PERSPECTIVE: The current studies provide evidence for involvement of gap junctions in spinal cord pain facilitation. Intrathecal carbenoxolone, a gap junction decoupler, reversed neuropathy-induced mirror image pain and intrathecal gp120-induced allodynia. In addition, it decreased gp120-induced proinflammatory cytokines. This suggests gap junction activation might lead to proinflammatory cytokine release by distantly activated glia. SN - 1526-5900 UR - https://www.unboundmedicine.com/medline/citation/15501197/Spinal_gap_junctions:_potential_involvement_in_pain_facilitation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1526-5900(04)00878-8 DB - PRIME DP - Unbound Medicine ER -