title: Effects of topical diclofenac plus heparin (DHEP+H plaster) on somatic pain sensitivity in healthy subjects with a latent algogenic condition of the lower limb.
abstract: OBJECTIVE
  To evaluate whether a diclofenac epolamine + heparin topical (plaster) is more effective than diclofenac plaster alone in reducing deep somatic hyperalgesia in subjects without spontaneous pain and whether the effect is linked to or independent of the anti-edematous action of heparin.
  
  
  METHODS
  Prospective, double-blind, randomized and controlled, four-arm parallel design trial.
  
  
  METHODS
  One hundred and four patients (84 women, 20 men, mean age 42.2 ± 13.3 years), with deep somatic hyperalgesia in one thigh, randomly assigned to one of 4 groups of 26 each.
  
  
  METHODS
  Each group underwent one of the following plaster treatments on one thigh: diclofenac+heparin; diclofenac; heparin; placebo, for 7 days, renewing the plaster every 24 hours.
  
  
  METHODS
  Before treatment (day 1), at day 4 and day 8, assessment of (a) pressure and electrical pain thresholds of vastus lateralis and overlying subcutis and skin; and (b) structure/thickness of subcutis and muscle with ultrasounds at the same level.
  
  
  RESULTS
  During treatment, in placebo and heparin, no significant threshold changes, except subcutis thresholds which increased slightly (P < 0.02); in diclofenac and diclofenac+heparin, significant increase in all thresholds (0.0001 < P < 0.04). Electrical muscle pain thresholds increased significantly more in diclofenac+heparin than in diclofenac, heparin, and placebo (0.0001 < P < 0.04). In all groups: no edema and thickness changes at ultrasounds in muscle and subcutis.
  
  
  CONCLUSIONS
  Topical diclofenac+heparin is significantly more effective than diclofenac alone in reducing muscle hyperalgesia in subjects without spontaneous pain, independently of the anti-edematous action of heparin. The results provide a rationale for the use of diclofenac+heparin also in algogenic conditions without evident signs of injury/edema/hematoma.
authors.affiliation: Ce.S.I., "G. D'Annunzio" Foundation, Chieti, Italy; Department of Medicine and Science of Aging, University of Chieti, Chieti, Italy.
authors.forename: Giannapia
authors.initials: G
authors.lastname: Affaitati
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fabrizio
authors.forename: Valeria
authors.initials: V
authors.lastname: Frangione
authors.forename: Arturo
authors.initials: A
authors.lastname: Lanzarotti
authors.forename: Mariangela
authors.initials: M
authors.lastname: Lopopolo
authors.forename: Emmanuele
authors.initials: E
authors.lastname: Tafuri
authors.forename: Domenico
authors.initials: D
authors.lastname: Lapenna
authors.forename: Maria Adele
authors.initials: MA
authors.lastname: Giamberardino
authors.forename: Raffaele
authors.initials: R
authors.lastname: Costantini
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000925:Anticoagulants / Q000627:therapeutic use*; D004008:Diclofenac / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004487:Edema / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology; D005260:Female; D064368:Healthy Volunteers; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D006930:Hyperalgesia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D059226:Nociceptive Pain / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D017288:Pain Threshold; D011446:Prospective Studies; D052097:Quadriceps Muscle / Q000000981:diagnostic imaging / Q000503:physiopathology*; D012867:Skin / Q000000981:diagnostic imaging / Q000503:physiopathology*; D013848:Thigh; D014463:Ultrasonography
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; C064142:diclofenac hydroxyethylpyrrolidine; D004008:Diclofenac; D006493:Heparin
keywords: RCT; deep somatic hyperalgesia; diclofenac plus heparin; pain thresholds; plaster; topical; ultrasound