title: Topical application of compound Ibuprofen suppresses pain by inhibiting sensory neuron hyperexcitability and neuroinflammation in a rat model of intervertebral foramen inflammation.
abstract: There is lack of evidence that topical application of an anti-inflammatory reagent could reduce pain due to intervertebral foramen (IVF) inflammation (IVFI). We investigated analgesic effects and underlying mechanisms of topical application of a compound ibuprofen cream (CIC) onto the surface of back skin covering the inflamed L(5) IVF in a rat model. Repetitive CIC treatment (~.54 g each treatment daily for 5 consecutive days) significantly reduces severity and duration of IVFI-induced thermal hyperalgesia and mechanical allodynia by 80 to 100% and 50 to 66%, respectively. Electrophysiological studies and Western blot analysis demonstrated that CIC treatment significantly inhibited hyperexcitability of the inflamed dorsal root ganglion (DRG) neurons and upregulation of Nav1.7 and Nav1.8 protein, respectively. Pathological manifestations of the inflamed DRG were also markedly improved following CIC treatment. Further, in the inflamed DRGs, phosphorylation and expression of transcription factor NF-κB and pro-inflammatory enzyme cyclooxygenase-2 (COX-2) were significantly increased, while a cytokine IL-1β level was increased. IVFI-induced upregulation of these molecules was significantly inhibited by CIC treatment. This study provides evidence that an anti-inflammatory reagent can be used topically to suppress pain due to IVFI and/or DRG inflammation through inhibition of sensory neuron hyperexcitability and the immune and inflammatory responses.
  
  
  CONCLUSIONS
  This study suggests a convenient and safe clinical intervention for treating pain due to intervertebral foramen inflammation and similar syndromes.
authors.affiliation: Department of Neurobiology, Parker Research Institute, 2500 Walnut Hill Lane, Dallas, TX 75229, USA.
authors.forename: Zhi-Jiang
authors.initials: ZJ
authors.lastname: Huang
authors.forename: Erica
authors.initials: E
authors.lastname: Hsu
authors.forename: Hao-Chuan
authors.initials: HC
authors.lastname: Li
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Rosner
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Rupert
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Song
mesh_terms: D000287:Administration, Topical; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005727:Ganglia, Spinal / Q000473:pathology; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D007052:Ibuprofen / Q000008:administration & dosage*; D007249:Inflammation / Q000150:complications* / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D007403:Intervertebral Disc; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D062556:NAV1.7 Voltage-Gated Sodium Channel; D062559:NAV1.8 Voltage-Gated Sodium Channel; D010146:Pain / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018712:Analgesics, Non-Narcotic; D053583:Interleukin-1beta; D062556:NAV1.7 Voltage-Gated Sodium Channel; D062559:NAV1.8 Voltage-Gated Sodium Channel; C568319:Scn10a protein, rat; C503480:Scn9a protein, rat; D015222:Sodium Channels; D007052:Ibuprofen