Newly Published
Pain Medicine  |   December 2017
Transcriptional Changes in Dorsal Spinal Cord Persist after Surgical Incision Despite Preemptive Analgesia with Peripheral Resiniferatoxin
Author Notes
  • From the Department of Perioperative Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland (S.J.R., M.R.S., D.M.L., M.J.I., A.J.M.); and the Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio (S.J.R.).
  • Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).
    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).×
  • This work has been presented in abstract form at the American Pain Society 36th Annual Scientific Meeting in May 2017 in Pittsburgh, Pennsylvania.
    This work has been presented in abstract form at the American Pain Society 36th Annual Scientific Meeting in May 2017 in Pittsburgh, Pennsylvania.×
  • Submitted for publication May 22, 2017. Accepted for publication October 26, 2017.
    Submitted for publication May 22, 2017. Accepted for publication October 26, 2017.×
  • Acknowledgments: The authors would like to thank Amelia Loydpierson, B.A., Department of Perioperative Medicine, Clinical Center, National Institutes of Health (NIH), Bethesda, Maryland, for her contributions to the immunohistochemical staining. Stephen J. Raithel, B.A., was supported by the NIH Medical Research Scholars Program, a public–private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation (New York, New York), the American Association for Dental Research (Alexandria, Virginia), the Colgate-Palmolive Company (New York, New York), Genentech (San Francisco, California), alumni of student research programs, and other individual supporters. The authors also acknowledge the early support of the National Center for Complementary and Integrative Health, NIH, Bethesda, Maryland.
    Acknowledgments: The authors would like to thank Amelia Loydpierson, B.A., Department of Perioperative Medicine, Clinical Center, National Institutes of Health (NIH), Bethesda, Maryland, for her contributions to the immunohistochemical staining. Stephen J. Raithel, B.A., was supported by the NIH Medical Research Scholars Program, a public–private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation (New York, New York), the American Association for Dental Research (Alexandria, Virginia), the Colgate-Palmolive Company (New York, New York), Genentech (San Francisco, California), alumni of student research programs, and other individual supporters. The authors also acknowledge the early support of the National Center for Complementary and Integrative Health, NIH, Bethesda, Maryland.×
  • Research Support: This work was supported by the intramural research program of the Clinical Center, National Institutes of Health (Bethesda, Maryland).
    Research Support: This work was supported by the intramural research program of the Clinical Center, National Institutes of Health (Bethesda, Maryland).×
  • Competing Interests: The authors declare no competing interests.
    Competing Interests: The authors declare no competing interests.×
  • Correspondence: Address correspondence to Dr. Iadarola: Department of Perioperative Medicine, Clinical Center, Building 10, Room 2C401, 10 Center Drive, MSC 1510, National Institutes of Health, Bethesda, Maryland 20892–1510. miadarol@cc.nih.gov. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Pain Medicine / Central and Peripheral Nervous Systems / Pain Medicine
Pain Medicine   |   December 2017
Transcriptional Changes in Dorsal Spinal Cord Persist after Surgical Incision Despite Preemptive Analgesia with Peripheral Resiniferatoxin
Anesthesiology Newly Published on December 21, 2017. doi:10.1097/ALN.0000000000002006
Anesthesiology Newly Published on December 21, 2017. doi:10.1097/ALN.0000000000002006
Abstract

Background: Peripheral nociceptors expressing the ion channel transient receptor potential cation channel, subfamily V, member 1, play an important role in mediating postoperative pain. Signaling from these nociceptors in the peri- and postoperative period can lead to plastic changes in the spinal cord and, when controlled, can yield analgesia. The transcriptomic changes in the dorsal spinal cord after surgery, and potential coupling to transient receptor potential cation channel, subfamily V, member 1–positive nociceptor signaling, remain poorly studied.

Methods: Resiniferatoxin was injected subcutaneously into rat hind paw several minutes before surgical incision to inactivate transient receptor potential cation channel, subfamily V, member 1–positive nerve terminals. The effects of resiniferatoxin on postincisional measures of pain were assessed through postoperative day 10 (n = 51). Transcriptomic changes in the dorsal spinal cord, with and without peripheral transient receptor potential cation channel, subfamily V, member 1–positive nerve terminal inactivation, were assessed by RNA sequencing (n = 22).

Results: Peripherally administered resiniferatoxin increased thermal withdrawal latency by at least twofold through postoperative day 4, increased mechanical withdrawal threshold by at least sevenfold through postoperative day 2, and decreased guarding score by 90% relative to vehicle control (P < 0.05). Surgical incision induced 70 genes in the dorsal horn, and these changes were specific to the ipsilateral dorsal horn. Gene induction with surgical incision persisted despite robust analgesia from resiniferatoxin pretreatment. Many of the genes induced were related to microglial activation, such as Cd11b and Iba1.

Conclusions: A single subcutaneous injection of resiniferatoxin before incision attenuated both evoked and nonevoked measures of postoperative pain. Surgical incision induced transcriptomic changes in the dorsal horn that persisted despite analgesia with resiniferatoxin, suggesting that postsurgical pain signals can be blocked without preventing transcription changes in the dorsal horn.