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Role of peripheral hyperpolarization-activated cyclic nucleotide-modulated channel pacemaker channels in acute and chronic pain models in the rat.
Neuroscience. 2007 Feb 23; 144(4):1477-85.N

Abstract

Hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channels contribute to rhythmic spontaneous activity in the heart and CNS. Ectopic spontaneous neuronal activity has been implicated in the development and maintenance of acute and chronic hyperalgesia, allodynia and spontaneous pain. Previously, we documented that systemic administration of ZD7288, a specific blocker of pacemaker current (I(h)), decreased ectopic activity in dorsal root ganglion (DRG) and reversed tactile allodynia in spinal nerve ligated (SNL) rats [Chaplan SR, Guo HQ, Lee DH, Luo L, Liu C, Kuei C, Velumian AA, Butler MP, Brown SM, Dubin AE (2003) Neuronal hyperpolarization-activated pacemaker channels drive neuropathic pain. J Neurosci 23:1169-1178]. Spontaneous pain is the chief clinical manifestation of peripheral nerve injury; however, a role for I(h) in spontaneous pain has not been described. Here, in further rat studies, we report that systemic administration of ZD7288 reversed spontaneous pain induced by mild thermal injury (MTI) and tactile allodynia induced by SNL and MTI. In contrast, ZD7288 did not reduce thermal hyperalgesia. An important locus of action appears to be in the skin since intraplantar (local) administration of ZD7288 completely suppressed tactile allodynia arising from MTI and SNL and reduced spontaneous pain due to MTI. Immunohistochemical staining of plantar skin sections detected HCN1-HCN4 expression in mechanosensory structures (e.g., Meissner's corpuscles and Merkel cells). Collectively, these data suggest that expression and modulation of I(h) in the peripheral nervous system, including specialized sensory structures, may play a significant role in sensory processing and contribute to spontaneous pain and tactile allodynia.

Authors+Show Affiliations

Johnson and Johnson Pharmaceutical Research and Development, LLC, 3210 Merryfield Row, San Diego, CA 92121, USA.No 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

Language

eng

PubMed ID

17196750

Citation

Luo, L, et al. "Role of Peripheral Hyperpolarization-activated Cyclic Nucleotide-modulated Channel Pacemaker Channels in Acute and Chronic Pain Models in the Rat." Neuroscience, vol. 144, no. 4, 2007, pp. 1477-85.
Luo L, Chang L, Brown SM, et al. Role of peripheral hyperpolarization-activated cyclic nucleotide-modulated channel pacemaker channels in acute and chronic pain models in the rat. Neuroscience. 2007;144(4):1477-85.
Luo, L., Chang, L., Brown, S. M., Ao, H., Lee, D. H., Higuera, E. S., Dubin, A. E., & Chaplan, S. R. (2007). Role of peripheral hyperpolarization-activated cyclic nucleotide-modulated channel pacemaker channels in acute and chronic pain models in the rat. Neuroscience, 144(4), 1477-85.
Luo L, et al. Role of Peripheral Hyperpolarization-activated Cyclic Nucleotide-modulated Channel Pacemaker Channels in Acute and Chronic Pain Models in the Rat. Neuroscience. 2007 Feb 23;144(4):1477-85. PubMed PMID: 17196750.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of peripheral hyperpolarization-activated cyclic nucleotide-modulated channel pacemaker channels in acute and chronic pain models in the rat. AU - Luo,L, AU - Chang,L, AU - Brown,S M, AU - Ao,H, AU - Lee,D H, AU - Higuera,E S, AU - Dubin,A E, AU - Chaplan,S R, Y1 - 2006/12/29/ PY - 2006/06/27/received PY - 2006/10/12/revised PY - 2006/10/19/accepted PY - 2007/1/2/pubmed PY - 2007/5/22/medline PY - 2007/1/2/entrez SP - 1477 EP - 85 JF - Neuroscience JO - Neuroscience VL - 144 IS - 4 N2 - Hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channels contribute to rhythmic spontaneous activity in the heart and CNS. Ectopic spontaneous neuronal activity has been implicated in the development and maintenance of acute and chronic hyperalgesia, allodynia and spontaneous pain. Previously, we documented that systemic administration of ZD7288, a specific blocker of pacemaker current (I(h)), decreased ectopic activity in dorsal root ganglion (DRG) and reversed tactile allodynia in spinal nerve ligated (SNL) rats [Chaplan SR, Guo HQ, Lee DH, Luo L, Liu C, Kuei C, Velumian AA, Butler MP, Brown SM, Dubin AE (2003) Neuronal hyperpolarization-activated pacemaker channels drive neuropathic pain. J Neurosci 23:1169-1178]. Spontaneous pain is the chief clinical manifestation of peripheral nerve injury; however, a role for I(h) in spontaneous pain has not been described. Here, in further rat studies, we report that systemic administration of ZD7288 reversed spontaneous pain induced by mild thermal injury (MTI) and tactile allodynia induced by SNL and MTI. In contrast, ZD7288 did not reduce thermal hyperalgesia. An important locus of action appears to be in the skin since intraplantar (local) administration of ZD7288 completely suppressed tactile allodynia arising from MTI and SNL and reduced spontaneous pain due to MTI. Immunohistochemical staining of plantar skin sections detected HCN1-HCN4 expression in mechanosensory structures (e.g., Meissner's corpuscles and Merkel cells). Collectively, these data suggest that expression and modulation of I(h) in the peripheral nervous system, including specialized sensory structures, may play a significant role in sensory processing and contribute to spontaneous pain and tactile allodynia. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/17196750/Role_of_peripheral_hyperpolarization_activated_cyclic_nucleotide_modulated_channel_pacemaker_channels_in_acute_and_chronic_pain_models_in_the_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(06)01392-3 DB - PRIME DP - Unbound Medicine ER -