Highlights
- •Development of injectable calcium phosphate cements loaded with local anesthetics.
- •Combined cements have the properties required for use in preclinical studies.
- •The CatWalk is an appropriate tool to study implanted analgesic biomaterials.
- •Cements could be part of the global pain management protocol after bone surgery.
Abstract
Postoperative pain after bone reconstruction is a serious complication that could
jeopardize the global success of a surgery. This pain must be controlled and minimized
during the first 3 to 4 postoperative days to prevent it from becoming chronic. In
this study, a critical-size bone defect was created at the femoral distal end of rats
and filled by an injectable calcium phosphate cement (CPC) loaded or not with local
anesthetics (bupivacaine or ropivacaine). A functional evaluation of the gait was
performed using the CatWalk system to compare the postoperative pain relief enhanced
by the different CPCs after such a bone filling surgery. The results demonstrated
significant pain relief during the short-term postoperative period, as shown by the
print area and intensity parameters of the operated paw. At 24 hours, the print area decreased by 65%, 42%, and 24%, and the intensity decreased
by 25%, 9%, and 1% for unloaded, ropivacaine-loaded, and bupivacaine-loaded CPCs,
respectively, compared with the preoperative values. Bupivacaine-loaded CPC provided
an earlier return to full functional recovery than ropivacaine-loaded CPC. Moreover,
the CPCs retained their biologic and mechanical properties. For all these reasons,
anesthetic-loaded CPCs could be part of the global pain management protocol after
bone reconstruction surgery such as iliac crest bone grafting procedures.
Perspective
Bupivacaine-loaded CPC provided an earlier return to full gait function than ropivacaine-loaded
CPC, with preserved bone filling properties. Such analgesic CPCs deserve further in
vivo investigation and may be part of the global pain management protocol after bone
reconstruction or bone augmentation surgery such as iliac crest bone grafting.
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to The Journal of PainAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
ASTM: Standard Test Method for Time of Setting of Hydraulic-Cement Paste by Gillmore Needles. ASTM C266-08, 2008.
- The Use of Calcium Phosphate Bone Cement in Fracture Treatment: A Meta-Analysis of Randomized Trials.J Bone Jt Surg-Am Vol. 2008; 90: 1186-1196
- Innovations in postoperative pain management: continuous infusion of local anesthetics.AORN J. 2007; 85 (quiz 915-18 ): 904-914
- A sensitive and reliable locomotor rating scale for open field testing in rats.J Neurotrauma. 1995; 12: 1-21
- Frequency, intensity, development and repercussions of postoperative pain as a function of the type of surgery.Ann Fr Anesth Reanim. 1998; 17: 471-493
- Digigait quantitation of gait dynamics in rat rheumatoid arthritis model.J Musculoskelet Neuronal Interact. 2009; 9: 89-98
- Antinociceptive efficacy of lacosamide in the monosodium iodoacetate rat model for osteoarthritis pain.Arthritis Res Ther. 2007; 9: R14
- Articaine for supplemental intraosseous anesthesia in patients with irreversible pulpitis.J Endod. 2006; 32: 1044-1047
- Technological issues for the development of more efficient calcium phosphate bone cements: A critical assessment.Biomaterials. 2005; 26: 6423-6429
- Biphasic calcium phosphate ceramics for bone reconstruction: A review of biological response.Acta Biomater. 2017; 53: 1-12
- A review of local anesthetic cardiotoxicity and treatment with lipid emulsion.Local and Regional Anesthesia. 2010; 3: 11-19
- Thermal and mechanical antinociceptive action of spinal vs peripherally administered clonidine in the rat inflamed knee joint model.Br J Anaesth. 1999; 83: 436-441
- Bupivacaine, levobupivacaine and ropivacaine: are they clinically different?.Best Pract Res Clin Anaesthesiol. 2005; 19: 247-268
- Pan H-C: Detection of subtle neurological alterations by the Catwalk XT gait analysis system.J Neuroengineering Rehabil. 2014; 11: 1
- Postoperative pain in ambulatory surgery.Anesth Analg. 1997; 85: 808-816
- Gait analysis as an objective measure in a chronic pain model.J Neurosci Methods. 2002; 116: 197-213
- Evaluation of buprenorphine in a postoperative pain model in rats.Comp Med. 2009; 59: 60-71
- The CatWalk gait analysis in assessment of both dynamic and static gait changes after adult rat sciatic nerve resection.J Neurosci Methods. 2007; 164: 120-130
- Gait analysis and pain response of two rodent models of osteoarthritis.Pharmacol Biochem Behav. 2011; 97: 603-610
- The CatWalk method: A detailed analysis of behavioral changes after acute inflammatory pain in the rat.J Neurosci Methods. 2007; 163: 9-16
- NSAIDs and fracture healing.Curr Opin Rheumatol. 2013; 25: 524-531
- New processing approaches in calcium phosphate cements and their applications in regenerative medicine.Acta Biomater. 2010; 6: 2863-2873
- Calcium phosphate cements as bone drug delivery systems: A review.J Controlled Release. 2006; 113: 102-110
- Autogenous iliac crest bone graft. Complications and functional assessment.Clin Orthop. 1997; 339: 76-81
- Automated Quantitative Gait Analysis During Overground Locomotion in the Rat: Its Application to Spinal Cord Contusion and Transection Injuries.J Neurotrauma. 2001; 18: 187-201
- Strain and locomotor speed affect over-ground locomotion in intact rats.Physiol Behav. 2007; 92: 993-1001
- Effects of Enriched Housing on Functional Recovery After Spinal Cord Contusive Injury in the Adult Rat.J Neurotrauma. 2001; 18: 203-215
- Anterior cervical discectomy and fusion (ACDF) autograft versus graft substitutes: what do patients prefer?—A clinical study.J Spine Surg. 2016; 2: 105-110
- Overlapping signatures of chronic pain in the DNA methylation landscape of prefrontal cortex and peripheral T cells.Sci Rep. 2016; 6: 19615
- Design and properties of novel gallium-doped injectable apatitic cements.Acta Biomater. 2015; 24: 322-332
- Assessment of Gait in a Rat Model of Myofascial Inflammation Using the CatWalk System: .Spine. 2011; 36: 1760-1764
- Using the CatWalk method to assess weight-bearing and pain behaviour in walking rats with ankle joint monoarthritis induced by carrageenan: Effects of morphine and rofecoxib.J Neurosci Methods. 2008; 174: 1-9
- Injectability, microstructure and release properties of sodium fusidate-loaded apatitic cement as a local drug-delivery system.Mater Sci Eng C. 2016; 59: 177-184
- Local delivery of bisphosphonate from coated orthopedic implants increases implants mechanical stability in osteoporotic rats.J Biomed Mater Res A. 2006; 76: 133-143
- Calcium phosphate drug delivery system: influence of local zoledronate release on bone implant osteointegration.Bone. 2005; 36: 52-60
- Donor site morbidity following iliac crest bone harvesting for cervical fusion: a comparison between minimally invasive and open techniques.Eur Spine J. 2008; 17: 845-852
- [Regional anaesthesia versus general anaesthesia-pathophysiology and clinical implications].Anaesthesiol Reanim. 2004; 29: 30-38
- Calcium phosphate biomaterials and bone mineral. Differences in composition, structures and properties.Biomaterials. 1990; 11: 13-15
- Comparison of Autogenous Bone Graft and Endothermic Calcium Phosphate Cement for Defect Augmentation in Tibial Plateau Fractures: A Multicenter, Prospective, Randomized Study.J Bone Jt Surg-Am Vol. 2008; 90: 2057-2061
- NSAID-induced Gastrointestinal Injury: A Focused Update for Clinicians.J Clin Gastroenterol. 2016; 50: 5-10
- Pain management: engineering successful outcomes.J Healthc Mater Manage. 1992; 10: 61-66
- Donor site morbidity after anterior iliac crest bone harvest for single-level anterior cervical discectomy and fusion.Spine. 2003; 28: 134-139
- A prospective cohort analysis of adjacent vertebral body bone mineral density in lumbar surgery patients with or without instrumented posterolateral fusion: a 9- to 12-year follow-up.Spine. 2005; 30: 1750-1755
- Pain after surgery.Br J Anaesth. 1991; 67: 233-234
- In vitro drug release of antibiotic-loaded porous hydroxyapatite cement.Artif Cells Blood Substit Biotechnol. 1995; 23: 81-88
- Automated quantitative gait analysis in animal models of movement disorders.BMC Neurosci. 2010; 11: 1
- Controlling the biological function of calcium phosphate bone substitutes with drugs.Acta Biomater. 2012; 8: 3541-3551
- Analgesic properties of calcium phosphate apatite loaded with bupivacaine on postoperative pain.J Biomed Mater Res B Appl Biomater. 2010; 94: 89-96
- In vivo bone augmentation in an osteoporotic environment using bisphosphonate-loaded calcium deficient apatite.Biomaterials. 2010; 31: 7776-7784
- Calcium phosphate biomaterials as bone drug delivery systems: a review.Drug Discov Today. 2010; 15: 547-552
- Vertebroplasty using bisphosphonate-loaded calcium phosphate cement in a standardized vertebral body bone defect in an osteoporotic sheep model.Acta Biomater. 2014; 10: 4887-4895
- ‘CatWalk'automated quantitative gait analysis as a novel method to assess mechanical allodynia in the rat; a comparison with von Frey testing.Pain. 2003; 102: 203-209
- Postoperative HyperalgesiaIts Clinical Importance and Relevance.J Am Soc Anesthesiol. 2006; 104: 601-607
- Early administration of oral morphine to orthopedic patients after surgery.J Opioid Manag. 2006; 2: 88-92
- Calcium phosphate cements for bone substitution: Chemistry, handling and mechanical properties.Acta Biomater. 2014; 10: 1035-1049
Article info
Publication history
Published online: May 14, 2018
Accepted:
April 26,
2018
Received in revised form:
December 23,
2017
Received:
August 5,
2017
Footnotes
☆Funding for this study was provided by the University of Nantes through the interdisciplinary “CAAPRO project 2015-67.”
✯✯The authors have no conflicts of interest to declare.
Identification
Copyright
© 2018 by the American Pain Society
