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Elbow denervation in dogs: Development of an in vivo surgical procedure and pilot testing
The Veterinary Journal 190 (2011) 220–224
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The Veterinary Journal journal homepage: www.elsevier.com/locate/tvjl
Elbow denervation in dogs: Development of an in vivo surgical procedure and pilot testing Helia Zamprogno a, Jon Hash a, Don A. Hulse b, B. Duncan X. Lascelles a,⇑ a b
Comparative Pain Research Laboratory, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA Department of Clinical Sciences, College of Veterinary Medicine, Texas A&M University, College Station, TX, USA
a r t i c l e
i n f o
Article history: Accepted 20 October 2010
Keywords: Dog Elbow Degenerative joint disease Pain Denervation
a b s t r a c t The objective of this study was to develop a surgical technique for sensory denervation of the canine elbow joint and to assess the effects of denervation on limb function in normal dogs. Twenty cadavers (40 elbows) were used to characterize innervation and design the surgical protocol which was tested in 13 cadavers (26 normal elbows). The effect of denervation on limb function was assessed in vivo in four dogs with the elbow randomly selected for the procedure. Primary outcome measures were static bodyweight distribution and distal limb mechanical sensory thresholds; secondary outcome measures were subjectively scored lameness, neurological function and pain on manipulation. Histology was performed on all resected tissues to determine whether nerves had been resected. Denervation was achieved by separate medial and lateral surgical approaches. In testing the developed surgical protocol, 111/130 resected samples contained nerve tissue in the healthy cadaveric elbows and 18/20 in the in vivo study. Limb function and sensation were not altered by elbow joint denervation. The protocol developed for denervation of the canine elbow appears feasible and does not result in any sensory or motor deficits of the forelimb. Ó 2010 Elsevier Ltd. All rights reserved.
Introduction Dogs are frequently affected by degenerative joint disease (DJD) (Johnston, 1997) but the options for treatment of DJD-associated elbow pain are limited. Medical management, primarily the use of non-steroidal anti-inflammatory drugs (NSAIDs), is the most common treatment modality (Johnston et al., 2008). However, elbow joint DJD-associated pain often does not respond well to systemic pain relief (Hercock et al., 2009). Surgical options include arthrodesis, which can alleviate pain but results in permanent mechanical lameness (De Haan et al., 1996), and total elbow joint replacement (Conzemius, 2009; Conzemius et al., 2001; Conzemius and Vandervoort, 2005; Cook and Payne, 1997; McKee et al., 2004), which has not yet been fully incorporated in the clinical setting. Denervation of the elbow has been described in humans and good outcomes have been observed (Dellon, 2009a,b;). To the authors’ knowledge the hip is the only joint where denervation has been described in veterinary medicine. Published reports of this procedure have described subjectively measured outcomes as ‘excellent’ (Ferrigno et al., 2007; Kinzel et al., 2002), but using objective force plate analysis, only 50% of dogs showed improved limb use (Lister et al., 2009). ⇑ Corresponding author. Tel.: +1 919 513 6762; fax: +1 919 513 6336. E-mail address: [email protected] (B. Duncan X. Lascelles). 1090-0233/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.tvjl.2010.10.015
The purpose of this study was to develop a surgical technique for denervation of the canine elbow and to determine if surgical denervation had an adverse effect on limb function in normal dogs. We hypothesized that an elbow denervation procedure could be designed and that the procedure would have no adverse effects on limb function or cutaneous sensation. Materials and methods Development and testing of a surgical protocol for elbow denervation Large mixed-breed, skeletally mature dogs, scheduled for euthanasia at a local animal shelter for the purposes of population control (i.e. unrelated to this study) were used. Thirty-three dogs (mean bodyweight 22.6 ± 4.5 kg) were used as follows: 12 cadavers (24 normal elbows) for gross characterization of innervation and anatomical relationships of the nerves to surrounding structures; 8 cadavers (16 normal elbows) to design the surgical approach and refine a protocol; 13 cadavers (26 normal elbows) to test the surgical denervation protocol in normal elbows. Dissection of forelimbs was performed on fresh specimens. A meticulous gross dissection of the musculocutaneous, median, ulnar and radial nerves was performed. The anatomy of the sensory branches of the nerves in relation to surrounding structures was carefully detailed with reference to previous anatomical reports (Ghoshal, 1975; Kitchell and Evans, 1993; König et al., 2007). Following this, a surgical approach for resection of sensory nerve branches going to the joint capsule was designed. This approach was practiced using 16 normal elbows, modified, and then tested (detailed description of the final surgical approach to denervation is described in Appendix A, Supplementary data). To test the technique, surgical denervation was performed on 26 normal cadaver elbows (13 right and 13 left) and sensory branches of each nerve resected. Following the resection
H. Zamprogno et al. / The Veterinary Journal 190 (2011) 220–224 of each nerve, the proximal portion of nerve tissue remaining was carefully stained using tissue dye. The resected tissue was retained for histology. Following resection, a wide exposure of the parent nerves allowed for accurate evaluation of where the resection was made. Resected portions were evaluated histologically (hematoxylin and eosin staining) to determine whether a defined nerve branch was present. All elbows were assessed by gross dissection following the procedure to determine if they were normal or had DJD.
In vivo pilot study of the adverse effects of surgical denervation Four purpose-bred hound dogs were used in this part of the study, which was approved by the Institutional Animal Care and Use Committee. The dogs were determined to be clinically healthy on the basis of a routine physical examination and the absence of orthopedic or neurologic abnormalities (as determined by an American College of Veterinary Surgeons [ACVS]-Board registered surgeon). After acclimatization to study personnel and procedures over a 2-week period, baseline values for the outcome measures were collected over the following 2 weeks. The outcome measures were as follows.
Static bodyweight distribution The percent bodyweight distribution (%BW(distrib)) was collected using a Pressure Sensitive Walkway as previously described (Lascelles et al., 2006, 2010). Ten sets of data (movies) were collected for each dog at each time point in each dog.
Sensory thresholds Each major autonomous zone (radial, musculocutaneous, ulna, combined median/ulna) was tested using custom forceps (TRUMP forceps) (Trumpatori et al., 2010). The mechanical response threshold at each of four cutaneous sites which corresponded with an area of skin supplied by each of the four major sensory nerves of the distal forelimb were collected as previously described (Trumpatori et al., 2010). Testing of each site was repeated three times at 2-min intervals.
Lameness scoring This was performed by a single assessor (HZ) using a visual analogue scale (VAS) where 0 corresponded to ‘sound’ and 100 to ‘non-weight bearing’ (subjective visual assessment).
Pain on manipulation The parameter was assessed by manual manipulation (full extension and flexion) of the elbow joint by a single assessor (HZ) scored as 0 (no resentment, normal amount of movement or wriggling), 1 (mild withdrawal, mildly resists), 2 (moderate withdrawal, body tenses, may orient to site, may vocalize), 3 (orients to site, forcible withdrawal from manipulation, may vocalize or bite) or 4 (tries to escape, prevents manipulation, bite, marked guarding of area).
Neurological evaluation of the forelimbs Subjective assessment of neurological function was performed by a single assessor (HZ). The evaluation included hopping, proprioception, tactile placing tactile, visual placing, wheel-barrowing, hemiwalking, and triceps, biceps and extensor carpi radialis reflexes of the forelimbs. Over a 2-week period (baseline data collection) static bodyweight distribution was collected on six separate days, sensory function data were collected on four separate days, and data on lameness, pain on manipulation and neurologic evaluation of the forelimbs were collected once three days prior to surgery. Following collection of baseline data, dogs were anesthetized for the surgical procedure. A mid-humeral brachial plexus block with bupivicaine (0.5 mg/kg laterally and 0.75 mg/kg medially; Trumpatori et al., 2010) was performed on the limb randomly selected for surgery. Surgery was performed as described in Appendix A (Supplementary data). The resected tissue was fixed in formalin and submitted for histopathology like for the cadaveric samples. Postoperatively, all outcome measures were collected on days 7, 14, 21 and 28 following surgery for each dog. Additionally, pain on manipulation of the operated elbow was assessed every 6 h for 24 h following surgery, then three times a day for 2 days, and once a day for the following 4 weeks. Buprenorphine (0.02 mg/kg IV) was administered postoperatively if required. Lameness and neurological status of the operated forelimbs were evaluated once a week for 4 weeks starting one week after the surgical procedure. Ampicillin (20 mg/kg PO, three times a day) was administered for 10 days to dogs with mild complications.
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Statistical analysis Descriptive statistics were used to describe the results of nerve resection in the cadavers. A Chi-square analysis was used to evaluate if there was a difference in the success of resection of nerve from left or right limb. For the %BW(distrib) and sensory thresholds, the operated/non-operated ratio of the values obtained for the operated leg and non-operated leg were calculated. All the preoperative data were used to calculate a single baseline ratio value (and standard deviation [SD]) for each outcome measure. The mean operated limb/non-operated limb ratios for each outcome measure at the four post-operative assessments (7, 14, 21, 28 days after surgery) were evaluated to determine if they lay within ±1SD (68.2% confidence interval [CI]) or ±2SDs (95.4% CI) of the baseline data. Lameness score, pain on manipulation of the operated elbow, and neurological status of the operated forelimb were described.
Results Part 1 Anatomical studies and a review of the literature were used to design the surgical protocol. Following the surgical approach, extensive dissection of the area and evaluation of the placement of the tissue dye indicated that the main nerve trunk was not surgically compromised in any limb tested. Histopathological evaluation of resected samples of tissue from 26 elbows showed that 111/130 resected portions of tissue had nerve present (Table 1). After the fourth cadaver (eight legs), histopathology revealed that the cranial radial nerve branch to the joint capsule was not being resected (only 2/8 positive). This led to an adjustment to the surgical resection at this particular site. The resection (immediately cranial to the lateral collateral ligament) extended more proximally and included a small part of the joint capsule. After this change, 14/18 cranial radial nerve branches to the joint capsule were resected (as determined by histopathology). There was no difference between left and right elbows for the number of positive samples (P = 0.99). Part 2 Four dogs, three males (Beagles) and one female (hound), were used in this part of the study. The ages were 2, 3 and 6 years old for the males and 4 years old for the female. The weights were 14, 10.4, 12.3, and 22 kg respectively. No complications were observed in the immediate post-operative period and limb function returned to normal by 6 h following the surgical procedure – the time that the preoperative regional block of motor function was expected to have worn off (Trumpatori et al., 2010). Histologically, 18/20 samples contained a defined nerve branch. In dogs 2 and 4, the median and the musculocutaneous nerve branches to the joint capsule, respectively, were not resected. For static bodyweight distribution, all post-operative mean ratio values lay within ±1 SD of the mean preoperative value (Table 2). Over the post-operative testing period, 7/64 sensory thresholds were outside the mean ±1 SD of the preoperative thresholds. Six of these were greater than the upper limit (decreased sensitivity of operated with respect to non-operated): one dog, musculocutaneous dermatome at day 7; one dog, ulnar nerve dermatome at days 14 and 21; one dog, ulnar nerve dermatome at day 21; one dog, median/ulnar dermatome at day 28. All post-operative mean ratio values lay within ±2 SDs of the mean preoperative value. The results are reported in Table 3. All dogs had a lameness score for each forelimb of 0 before the surgery. At 7, 14, 21 and 28 days following elbow denervation, the lameness score for each forelimb of each dog was 0. Pain on manipulation and palpation of the elbow joint was recognized only within the first 24 h. Dogs 2 and 4 scored 1 at 12 h; dog 4 was scored as 2 at 18 h; dog 4 was scored as 1 at 24. Pain scores were 0 at all time points for dogs 1 and 3. No pain was observed on manipulation of
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H. Zamprogno et al. / The Veterinary Journal 190 (2011) 220–224
Table 1 Histopathological evaluation of resected tissue samples from 26 normal cadaveric elbows. Histological evidence of nerve tissue was observed in 111/130 samples; Ø = no nerve seen histologically; + = nerve branch seen histologically in the resected sample. Dog #
Left ulnar
Left median
Left musculocutaneous
Left radial (cr)
Left radial (ca)
Right ulnar
Right median
Right musculocutaneous
Right radial (cr)
Right radial (ca)
1 2 3 4 5 6 7 8 9 10 11 12 13
+ Ø Ø + + + + + + + + + +
+ + + Ø + + + + + + + + +
+ + + + Ø + + + + + + + +
+ Ø Ø Ø + + + Ø + + + + +
+ + + + + + + + + + + + +
+ + + + + + + + + + Ø + +
Ø + + + Ø + + + + + + + +
Ø + + + + + + + Ø + + + +
Ø Ø + Ø Ø + + Ø Ø + + + +
+ + + + + + + + + + + + +
Table 2 Mean percentage bodyweight distribution (%BW(distrib)) ratios of the operated to non-operated forelimb for each dog. The 68.2% CI (1 SD) of the preoperative data is shown. All post-operative values (Days 7, 14, 21 and 28) lay within the ±1 SD of the preoperative mean value for each dog. Dog
Preoperative ratio
SD
68.4% CI
Day 7
Day 14
Day 21
Day 28
1 2 3 4
0.849 1.104 1.091 1.135
0.269 0.349 0.343 0.332
0.580–1.119 0.755–1.453 0.749–1.434 0.803–1.467
0.775 1.131 0.980 0.904
0.874 1.197 1.175 0.995
1.036 1.316 1.039 0.919
0.887 1.163 1.334 0.952
Table 3 Mean sensory threshold ratios (operated to non-operated ratios) for the radial (a), ulnar (b), musculocutaneous (c) and median/ulnar (d) dermatomes for each dog. The 68.2% CI (1 SD) of the preoperative data is shown. Post-operative values with an asterix () lay outside the ±1 SD of the preoperative mean value for each dog, but all values lay within ±2 SD of the mean preoperative threshold value. Dog
Baseline
SD
a 1 2 3 4
1.090 1.249 1.266 1.071
1.001 0.816 0.843 1.084
b 1 2 3 4
1.217 1.388 1.257 1.010
c 1 2 3 4 d 1 2 3 4
68.4% CI
Day 7
Day 14
Day 21
Day 28
0.088–2.092 0.431–2.064 0.423–2.109 0.013 to 2.156
0.616 0.281* 0.959 1.035
0.789 1.570 0.923 1.346
1.508 0.983 0.764 0.987
0.538 0.794 0.845 1.472
0.710 1.121 0.827 0.792
0.506–1.927 0.267–2.510 0.431–2.084 0.218–1.802
2.252* 0.460 1.970 1.203
0.89 0.940 0.699 1.05
0.846 0.672 0.552 1.043
0.996 1.729 1.139 1.316
1.063 0.917 1.143 1.507
1.160 0.419 0.599 0.962
0.096 to 2.223 0.498–1.336 0.544–1.742 0.544–2.469
1.045 0.763 1.703 0.161
1.385 1.552* 0.803 0.299
0.841 1.584* 1.963* 0.941
1.077 0.936 0.968 1.143
1.069 1.601 0.935 1.046
0.823 1.610 0.512 0.836
0.246–1.892 0.009 to 3.211 0.422–1.447 0.210–1.883
1.163 0.485 0.629 0.861
1.540 0.400 1.415 0.490
0.794 1.956 1.861* 0.660
0.902 1.073 1.725* 1.941
the elbow joint in any of the dogs after the first 24 h. Analgesia was administered to dog 4 at 18 h. During neurological examination, no abnormalities were observed in any of the dogs either preoperatively or at any assessment time point following elbow denervation. Post-operative complications included seroma formation in three dogs, which were treated conservatively with cage rest and warm packing for 10 min twice a day until resolved. Suture dehiscence on the lateral side was observed in dog 3, 3 days after surgery. The sutures were replaced and no further complications were observed in this dog.
Discussion The current study has defined an approach to denervation of the canine elbow and, using a pilot group of dogs, has shown that there were no detectable adverse effects on limb function. However, the effect of the procedure described here on pain in the DJD elbow is unknown. Although no adverse effects on limb function or cutaneous sensation were detected, the methods of evaluation of limb function (subjective VAS scale and the use of %BW(distrib) ratios between the forelimbs) have not yet been validated as limb use
H. Zamprogno et al. / The Veterinary Journal 190 (2011) 220–224
assessment methods. Further work needs to be done to evaluate the effects on limb use. The determination of the relationship between the muscles of the forelimb, the main nerves and the branches that innervate the muscles and elbow joint capsule was key to designing an approach to resection of the sensory nerve branches that supply the joint capsule. In contrast to a previous cadaveric study in humans (Bekler et al., 2008), there appeared to be consistency regarding the location and number of visualized branches innervating the joint capsule. Histopathology did not differentiate between sensory and motor nerves. Histopathology was used to confirm that nerve tissue was resected in each surgical site. In future studies, an immunohistochemical assessment could be used to allow for specific identification of sensory innervation using a combination of Protein Gene Product 9.5 (PGP9.5) to identify nerves, and calcitonin gene-related peptide (CGRP) and substance P (SP) to identify sensory nerves (Arrighi et al., 2008; Brown et al., 1997; Hoover et al., 2008). The in vivo study indicated that the main nerve trunks were not compromised, since motor innervation to the distal forelimb and sensory innervation to distal cutaneous dermatomes appeared to be preserved. As nerve tissue was resected during the procedure, we assume that the surgical approach did in fact target sensory nerve branches to the joint capsule. Further work is needed to determine whether or not joint sensation is actually decreased. Denervation of the elbow joint as described here will only provide clinical benefit if a significant source of pain is the soft tissue structures of the synovium and joint capsule. Recent studies have emphasized the increased sensory innervation of soft tissue structures in painful arthritic joints in humans (Saxler et al., 2007; Szadek et al., 2010), but recent information has highlighted the possibility that subchondral bone may be a significant contributor to joint pain in osteoarthritis (Niv et al., 2003; Ogino et al., 2009). Further studies are needed to determine (1) the sensory contribution of each branch to the joint capsule, (2) if the anatomical changes of a DJD-affected joint will interfere with the surgical approach, and (3) if sensory innervation of DJD-affected joints is altered (i.e. there are more numerous sensory branches than in normal joints). Finally, although there is evidence indicating that sensory denervation may decrease joint inflammation in inflammatory arthritis (Kane et al., 2005), the long-term effects of capsular denervation on the progression of osteoarthritis need to be evaluated.
Conclusions Limb function and sensation were not altered by elbow joint denervation. The developed protocol for denervation of the canine elbow appears feasible and does not result in any sensory or motor deficits of the forelimb.
Conflict of interest statement None of the authors of this paper has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of the paper.
Acknowledgements The authors would like to thank Alice Harvey for the illustrations. The study was funded from accrued salary release (Duncan Lascelles).
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Saxler, G., Loer, F., Skumavc, M., Pfortner, J., Hanesch, U., 2007. Localization of SPand CGRP-immunopositive nerve fibers in the hip joint of patients with painful osteoarthritis and of patients with painless failed total hip arthroplasties. European Journal of Pain 11, 67–74. Szadek, K.M., Hoogland, P.V., Zuurmond, W.W., De Lange, J.J., Perez, R.S., 2010. Possible nociceptive structures in the sacroiliac joint cartilage: an immunohistochemical study. Clinical Anatomy 23, 192–198.
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Contents lists available at ScienceDirect
The Veterinary Journal journal homepage: www.elsevier.com/locate/tvjl
Elbow denervation in dogs: Development of an in vivo surgical procedure and pilot testing Helia Zamprogno a, Jon Hash a, Don A. Hulse b, B. Duncan X. Lascelles a,⇑ a b
Comparative Pain Research Laboratory, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA Department of Clinical Sciences, College of Veterinary Medicine, Texas A&M University, College Station, TX, USA
a r t i c l e
i n f o
Article history: Accepted 20 October 2010
Keywords: Dog Elbow Degenerative joint disease Pain Denervation
a b s t r a c t The objective of this study was to develop a surgical technique for sensory denervation of the canine elbow joint and to assess the effects of denervation on limb function in normal dogs. Twenty cadavers (40 elbows) were used to characterize innervation and design the surgical protocol which was tested in 13 cadavers (26 normal elbows). The effect of denervation on limb function was assessed in vivo in four dogs with the elbow randomly selected for the procedure. Primary outcome measures were static bodyweight distribution and distal limb mechanical sensory thresholds; secondary outcome measures were subjectively scored lameness, neurological function and pain on manipulation. Histology was performed on all resected tissues to determine whether nerves had been resected. Denervation was achieved by separate medial and lateral surgical approaches. In testing the developed surgical protocol, 111/130 resected samples contained nerve tissue in the healthy cadaveric elbows and 18/20 in the in vivo study. Limb function and sensation were not altered by elbow joint denervation. The protocol developed for denervation of the canine elbow appears feasible and does not result in any sensory or motor deficits of the forelimb. Ó 2010 Elsevier Ltd. All rights reserved.
Introduction Dogs are frequently affected by degenerative joint disease (DJD) (Johnston, 1997) but the options for treatment of DJD-associated elbow pain are limited. Medical management, primarily the use of non-steroidal anti-inflammatory drugs (NSAIDs), is the most common treatment modality (Johnston et al., 2008). However, elbow joint DJD-associated pain often does not respond well to systemic pain relief (Hercock et al., 2009). Surgical options include arthrodesis, which can alleviate pain but results in permanent mechanical lameness (De Haan et al., 1996), and total elbow joint replacement (Conzemius, 2009; Conzemius et al., 2001; Conzemius and Vandervoort, 2005; Cook and Payne, 1997; McKee et al., 2004), which has not yet been fully incorporated in the clinical setting. Denervation of the elbow has been described in humans and good outcomes have been observed (Dellon, 2009a,b;). To the authors’ knowledge the hip is the only joint where denervation has been described in veterinary medicine. Published reports of this procedure have described subjectively measured outcomes as ‘excellent’ (Ferrigno et al., 2007; Kinzel et al., 2002), but using objective force plate analysis, only 50% of dogs showed improved limb use (Lister et al., 2009). ⇑ Corresponding author. Tel.: +1 919 513 6762; fax: +1 919 513 6336. E-mail address: [email protected] (B. Duncan X. Lascelles). 1090-0233/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.tvjl.2010.10.015
The purpose of this study was to develop a surgical technique for denervation of the canine elbow and to determine if surgical denervation had an adverse effect on limb function in normal dogs. We hypothesized that an elbow denervation procedure could be designed and that the procedure would have no adverse effects on limb function or cutaneous sensation. Materials and methods Development and testing of a surgical protocol for elbow denervation Large mixed-breed, skeletally mature dogs, scheduled for euthanasia at a local animal shelter for the purposes of population control (i.e. unrelated to this study) were used. Thirty-three dogs (mean bodyweight 22.6 ± 4.5 kg) were used as follows: 12 cadavers (24 normal elbows) for gross characterization of innervation and anatomical relationships of the nerves to surrounding structures; 8 cadavers (16 normal elbows) to design the surgical approach and refine a protocol; 13 cadavers (26 normal elbows) to test the surgical denervation protocol in normal elbows. Dissection of forelimbs was performed on fresh specimens. A meticulous gross dissection of the musculocutaneous, median, ulnar and radial nerves was performed. The anatomy of the sensory branches of the nerves in relation to surrounding structures was carefully detailed with reference to previous anatomical reports (Ghoshal, 1975; Kitchell and Evans, 1993; König et al., 2007). Following this, a surgical approach for resection of sensory nerve branches going to the joint capsule was designed. This approach was practiced using 16 normal elbows, modified, and then tested (detailed description of the final surgical approach to denervation is described in Appendix A, Supplementary data). To test the technique, surgical denervation was performed on 26 normal cadaver elbows (13 right and 13 left) and sensory branches of each nerve resected. Following the resection
H. Zamprogno et al. / The Veterinary Journal 190 (2011) 220–224 of each nerve, the proximal portion of nerve tissue remaining was carefully stained using tissue dye. The resected tissue was retained for histology. Following resection, a wide exposure of the parent nerves allowed for accurate evaluation of where the resection was made. Resected portions were evaluated histologically (hematoxylin and eosin staining) to determine whether a defined nerve branch was present. All elbows were assessed by gross dissection following the procedure to determine if they were normal or had DJD.
In vivo pilot study of the adverse effects of surgical denervation Four purpose-bred hound dogs were used in this part of the study, which was approved by the Institutional Animal Care and Use Committee. The dogs were determined to be clinically healthy on the basis of a routine physical examination and the absence of orthopedic or neurologic abnormalities (as determined by an American College of Veterinary Surgeons [ACVS]-Board registered surgeon). After acclimatization to study personnel and procedures over a 2-week period, baseline values for the outcome measures were collected over the following 2 weeks. The outcome measures were as follows.
Static bodyweight distribution The percent bodyweight distribution (%BW(distrib)) was collected using a Pressure Sensitive Walkway as previously described (Lascelles et al., 2006, 2010). Ten sets of data (movies) were collected for each dog at each time point in each dog.
Sensory thresholds Each major autonomous zone (radial, musculocutaneous, ulna, combined median/ulna) was tested using custom forceps (TRUMP forceps) (Trumpatori et al., 2010). The mechanical response threshold at each of four cutaneous sites which corresponded with an area of skin supplied by each of the four major sensory nerves of the distal forelimb were collected as previously described (Trumpatori et al., 2010). Testing of each site was repeated three times at 2-min intervals.
Lameness scoring This was performed by a single assessor (HZ) using a visual analogue scale (VAS) where 0 corresponded to ‘sound’ and 100 to ‘non-weight bearing’ (subjective visual assessment).
Pain on manipulation The parameter was assessed by manual manipulation (full extension and flexion) of the elbow joint by a single assessor (HZ) scored as 0 (no resentment, normal amount of movement or wriggling), 1 (mild withdrawal, mildly resists), 2 (moderate withdrawal, body tenses, may orient to site, may vocalize), 3 (orients to site, forcible withdrawal from manipulation, may vocalize or bite) or 4 (tries to escape, prevents manipulation, bite, marked guarding of area).
Neurological evaluation of the forelimbs Subjective assessment of neurological function was performed by a single assessor (HZ). The evaluation included hopping, proprioception, tactile placing tactile, visual placing, wheel-barrowing, hemiwalking, and triceps, biceps and extensor carpi radialis reflexes of the forelimbs. Over a 2-week period (baseline data collection) static bodyweight distribution was collected on six separate days, sensory function data were collected on four separate days, and data on lameness, pain on manipulation and neurologic evaluation of the forelimbs were collected once three days prior to surgery. Following collection of baseline data, dogs were anesthetized for the surgical procedure. A mid-humeral brachial plexus block with bupivicaine (0.5 mg/kg laterally and 0.75 mg/kg medially; Trumpatori et al., 2010) was performed on the limb randomly selected for surgery. Surgery was performed as described in Appendix A (Supplementary data). The resected tissue was fixed in formalin and submitted for histopathology like for the cadaveric samples. Postoperatively, all outcome measures were collected on days 7, 14, 21 and 28 following surgery for each dog. Additionally, pain on manipulation of the operated elbow was assessed every 6 h for 24 h following surgery, then three times a day for 2 days, and once a day for the following 4 weeks. Buprenorphine (0.02 mg/kg IV) was administered postoperatively if required. Lameness and neurological status of the operated forelimbs were evaluated once a week for 4 weeks starting one week after the surgical procedure. Ampicillin (20 mg/kg PO, three times a day) was administered for 10 days to dogs with mild complications.
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Statistical analysis Descriptive statistics were used to describe the results of nerve resection in the cadavers. A Chi-square analysis was used to evaluate if there was a difference in the success of resection of nerve from left or right limb. For the %BW(distrib) and sensory thresholds, the operated/non-operated ratio of the values obtained for the operated leg and non-operated leg were calculated. All the preoperative data were used to calculate a single baseline ratio value (and standard deviation [SD]) for each outcome measure. The mean operated limb/non-operated limb ratios for each outcome measure at the four post-operative assessments (7, 14, 21, 28 days after surgery) were evaluated to determine if they lay within ±1SD (68.2% confidence interval [CI]) or ±2SDs (95.4% CI) of the baseline data. Lameness score, pain on manipulation of the operated elbow, and neurological status of the operated forelimb were described.
Results Part 1 Anatomical studies and a review of the literature were used to design the surgical protocol. Following the surgical approach, extensive dissection of the area and evaluation of the placement of the tissue dye indicated that the main nerve trunk was not surgically compromised in any limb tested. Histopathological evaluation of resected samples of tissue from 26 elbows showed that 111/130 resected portions of tissue had nerve present (Table 1). After the fourth cadaver (eight legs), histopathology revealed that the cranial radial nerve branch to the joint capsule was not being resected (only 2/8 positive). This led to an adjustment to the surgical resection at this particular site. The resection (immediately cranial to the lateral collateral ligament) extended more proximally and included a small part of the joint capsule. After this change, 14/18 cranial radial nerve branches to the joint capsule were resected (as determined by histopathology). There was no difference between left and right elbows for the number of positive samples (P = 0.99). Part 2 Four dogs, three males (Beagles) and one female (hound), were used in this part of the study. The ages were 2, 3 and 6 years old for the males and 4 years old for the female. The weights were 14, 10.4, 12.3, and 22 kg respectively. No complications were observed in the immediate post-operative period and limb function returned to normal by 6 h following the surgical procedure – the time that the preoperative regional block of motor function was expected to have worn off (Trumpatori et al., 2010). Histologically, 18/20 samples contained a defined nerve branch. In dogs 2 and 4, the median and the musculocutaneous nerve branches to the joint capsule, respectively, were not resected. For static bodyweight distribution, all post-operative mean ratio values lay within ±1 SD of the mean preoperative value (Table 2). Over the post-operative testing period, 7/64 sensory thresholds were outside the mean ±1 SD of the preoperative thresholds. Six of these were greater than the upper limit (decreased sensitivity of operated with respect to non-operated): one dog, musculocutaneous dermatome at day 7; one dog, ulnar nerve dermatome at days 14 and 21; one dog, ulnar nerve dermatome at day 21; one dog, median/ulnar dermatome at day 28. All post-operative mean ratio values lay within ±2 SDs of the mean preoperative value. The results are reported in Table 3. All dogs had a lameness score for each forelimb of 0 before the surgery. At 7, 14, 21 and 28 days following elbow denervation, the lameness score for each forelimb of each dog was 0. Pain on manipulation and palpation of the elbow joint was recognized only within the first 24 h. Dogs 2 and 4 scored 1 at 12 h; dog 4 was scored as 2 at 18 h; dog 4 was scored as 1 at 24. Pain scores were 0 at all time points for dogs 1 and 3. No pain was observed on manipulation of
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Table 1 Histopathological evaluation of resected tissue samples from 26 normal cadaveric elbows. Histological evidence of nerve tissue was observed in 111/130 samples; Ø = no nerve seen histologically; + = nerve branch seen histologically in the resected sample. Dog #
Left ulnar
Left median
Left musculocutaneous
Left radial (cr)
Left radial (ca)
Right ulnar
Right median
Right musculocutaneous
Right radial (cr)
Right radial (ca)
1 2 3 4 5 6 7 8 9 10 11 12 13
+ Ø Ø + + + + + + + + + +
+ + + Ø + + + + + + + + +
+ + + + Ø + + + + + + + +
+ Ø Ø Ø + + + Ø + + + + +
+ + + + + + + + + + + + +
+ + + + + + + + + + Ø + +
Ø + + + Ø + + + + + + + +
Ø + + + + + + + Ø + + + +
Ø Ø + Ø Ø + + Ø Ø + + + +
+ + + + + + + + + + + + +
Table 2 Mean percentage bodyweight distribution (%BW(distrib)) ratios of the operated to non-operated forelimb for each dog. The 68.2% CI (1 SD) of the preoperative data is shown. All post-operative values (Days 7, 14, 21 and 28) lay within the ±1 SD of the preoperative mean value for each dog. Dog
Preoperative ratio
SD
68.4% CI
Day 7
Day 14
Day 21
Day 28
1 2 3 4
0.849 1.104 1.091 1.135
0.269 0.349 0.343 0.332
0.580–1.119 0.755–1.453 0.749–1.434 0.803–1.467
0.775 1.131 0.980 0.904
0.874 1.197 1.175 0.995
1.036 1.316 1.039 0.919
0.887 1.163 1.334 0.952
Table 3 Mean sensory threshold ratios (operated to non-operated ratios) for the radial (a), ulnar (b), musculocutaneous (c) and median/ulnar (d) dermatomes for each dog. The 68.2% CI (1 SD) of the preoperative data is shown. Post-operative values with an asterix () lay outside the ±1 SD of the preoperative mean value for each dog, but all values lay within ±2 SD of the mean preoperative threshold value. Dog
Baseline
SD
a 1 2 3 4
1.090 1.249 1.266 1.071
1.001 0.816 0.843 1.084
b 1 2 3 4
1.217 1.388 1.257 1.010
c 1 2 3 4 d 1 2 3 4
68.4% CI
Day 7
Day 14
Day 21
Day 28
0.088–2.092 0.431–2.064 0.423–2.109 0.013 to 2.156
0.616 0.281* 0.959 1.035
0.789 1.570 0.923 1.346
1.508 0.983 0.764 0.987
0.538 0.794 0.845 1.472
0.710 1.121 0.827 0.792
0.506–1.927 0.267–2.510 0.431–2.084 0.218–1.802
2.252* 0.460 1.970 1.203
0.89 0.940 0.699 1.05
0.846 0.672 0.552 1.043
0.996 1.729 1.139 1.316
1.063 0.917 1.143 1.507
1.160 0.419 0.599 0.962
0.096 to 2.223 0.498–1.336 0.544–1.742 0.544–2.469
1.045 0.763 1.703 0.161
1.385 1.552* 0.803 0.299
0.841 1.584* 1.963* 0.941
1.077 0.936 0.968 1.143
1.069 1.601 0.935 1.046
0.823 1.610 0.512 0.836
0.246–1.892 0.009 to 3.211 0.422–1.447 0.210–1.883
1.163 0.485 0.629 0.861
1.540 0.400 1.415 0.490
0.794 1.956 1.861* 0.660
0.902 1.073 1.725* 1.941
the elbow joint in any of the dogs after the first 24 h. Analgesia was administered to dog 4 at 18 h. During neurological examination, no abnormalities were observed in any of the dogs either preoperatively or at any assessment time point following elbow denervation. Post-operative complications included seroma formation in three dogs, which were treated conservatively with cage rest and warm packing for 10 min twice a day until resolved. Suture dehiscence on the lateral side was observed in dog 3, 3 days after surgery. The sutures were replaced and no further complications were observed in this dog.
Discussion The current study has defined an approach to denervation of the canine elbow and, using a pilot group of dogs, has shown that there were no detectable adverse effects on limb function. However, the effect of the procedure described here on pain in the DJD elbow is unknown. Although no adverse effects on limb function or cutaneous sensation were detected, the methods of evaluation of limb function (subjective VAS scale and the use of %BW(distrib) ratios between the forelimbs) have not yet been validated as limb use
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assessment methods. Further work needs to be done to evaluate the effects on limb use. The determination of the relationship between the muscles of the forelimb, the main nerves and the branches that innervate the muscles and elbow joint capsule was key to designing an approach to resection of the sensory nerve branches that supply the joint capsule. In contrast to a previous cadaveric study in humans (Bekler et al., 2008), there appeared to be consistency regarding the location and number of visualized branches innervating the joint capsule. Histopathology did not differentiate between sensory and motor nerves. Histopathology was used to confirm that nerve tissue was resected in each surgical site. In future studies, an immunohistochemical assessment could be used to allow for specific identification of sensory innervation using a combination of Protein Gene Product 9.5 (PGP9.5) to identify nerves, and calcitonin gene-related peptide (CGRP) and substance P (SP) to identify sensory nerves (Arrighi et al., 2008; Brown et al., 1997; Hoover et al., 2008). The in vivo study indicated that the main nerve trunks were not compromised, since motor innervation to the distal forelimb and sensory innervation to distal cutaneous dermatomes appeared to be preserved. As nerve tissue was resected during the procedure, we assume that the surgical approach did in fact target sensory nerve branches to the joint capsule. Further work is needed to determine whether or not joint sensation is actually decreased. Denervation of the elbow joint as described here will only provide clinical benefit if a significant source of pain is the soft tissue structures of the synovium and joint capsule. Recent studies have emphasized the increased sensory innervation of soft tissue structures in painful arthritic joints in humans (Saxler et al., 2007; Szadek et al., 2010), but recent information has highlighted the possibility that subchondral bone may be a significant contributor to joint pain in osteoarthritis (Niv et al., 2003; Ogino et al., 2009). Further studies are needed to determine (1) the sensory contribution of each branch to the joint capsule, (2) if the anatomical changes of a DJD-affected joint will interfere with the surgical approach, and (3) if sensory innervation of DJD-affected joints is altered (i.e. there are more numerous sensory branches than in normal joints). Finally, although there is evidence indicating that sensory denervation may decrease joint inflammation in inflammatory arthritis (Kane et al., 2005), the long-term effects of capsular denervation on the progression of osteoarthritis need to be evaluated.
Conclusions Limb function and sensation were not altered by elbow joint denervation. The developed protocol for denervation of the canine elbow appears feasible and does not result in any sensory or motor deficits of the forelimb.
Conflict of interest statement None of the authors of this paper has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of the paper.
Acknowledgements The authors would like to thank Alice Harvey for the illustrations. The study was funded from accrued salary release (Duncan Lascelles).
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