Management of chronic pain in whiplash injury
Alpar, Emin K
We investigated the response of chronic neck and shoulder pain to decompression of the carpal
tunnel in 38 patients with whiplash injury. We also determined the plasma levels of substance P (SP) and calcitonin gene-related peptide (CGRP), which are inflammatory peptides that sensitise nociceptors.
Compared with normal control subjects, the mean concentrations of SP (220 v 28 ng/l; p
After operation their levels fell to normal. There was resolution of neurological symptoms with improvement of pain in 90% of patients. Only two of the 30 with chronic neck and shoulder pain who had been treated conservatively showed improvement when followed up at two years.
In spite of having neuropathic pain arising from the median nerve, all these patients had normal electromyographic and nerve-conduction studies.
Chronic pain in whiplash injury may be caused by ‘atypical’ carpal tunnel syndrome and responds favourably to surgery which is indicated in patients with neck, shoulder and arm pain but not in those with mild symptoms in the hand. Previously, the presence of persistent neurological symptoms has been accepted as a sign of a poor outcome after a whiplash injury, but our study suggests that it may be possible to treat chronic pain by carpal tunnel decompression.
J Bone Joint Surg [Br] 2002;84-B:807-11. Received 13 August 2001; Accepted after revision 9 January 2002
Whiplash injury is a challenging condition to treat since the underlying pathology is poorly understood. The prognosis is adversely affected in the presence of persistent neurological signs, which are often not typically radicular. Many patients suffer disability because of chronic pain which affects their daily work and leisure activities. Some clinicians, members of the insurance industry and defence lawyers have advanced the concepts of secondary gain and compensation neurosis in such patients.1-4 In some the cause of chronic neck and shoulder pain has been ascribed to carpal tunnel syndrome 5 and Ide et al6 recently described entrapment of the brachial plexus and of peripheral nerves, including the median nerve at the carpal tunnel, after whiplash injury. They stated that nerve entrapment may cause severe symptoms and their persistence is associated with a poor outcome. Neurophysiological studies are normal in nerve entrapment caused by whiplash injury.5’6 Chronic pain after whiplash injury has been thought to arise from the posterior facet joints7 and also from damage to discs and ligaments.8
Pain is elicited by A-delta and C nociceptor fibres. Chronic pain may be caused by inflammatory factors which sensitise nociceptors in association with microneural damage. Sensory neurones projecting to laminae I and II of the superficial dorsal horn express the nociceptor peptides, calcitonin gene-related peptide (CGRP) and substance P (SP).9,10 The latter is a snesory peptide and plays an important role in pain sensation while (CGRP is a powerful vasodilating agent found in small sensory neurones and colocalised with SP. It is also a neurotransmitter and plays a significant part in sensory transmission.
In this prospective study we have investigated the levels of SP and CGRP before and after surgery for chronic neck and shoulder pain after whiplash injury. The clinical and functional outcomes after decompression of the median nerve at the carpal tunnel were also evaluated.
Patients and Methods
We treated 38 patients with chronic pain after whiplash injury by decompression of the carpal tunnel. A further 30 with similar signs and symptoms were treated conservatively and they served as a control group. The mean followup was for 18 months (12 to 24). There were ten men and 28 women in the surgical group with a mean age of 37.5 years. In the control group there were 12 men and 18 women with a mean age of 34.2 years. All the patients had been either drivers or passengers and stated that they had been wearing seat-belts. They all had developed symptoms and signs of atypical carpal tunnel syndrome as a result of the injury. They had peripheral symptoms within the area of the median nerve in addition to pain in the neck and shoulder. Routine clinical and neurological examination included assessment of the range of movements of the neck, focal tenderness, and changes in sensation and power in the upper limb. All patients had received physiotherapy in the form of either exercises for the release of nerve tension or cervical traction, and some had undergone acupuncture. Many had had osteopathic treatment and some used a transcutaneous electrical nerve-stimulator. All took non-steroidal anti-inflammatory drugs and had worn a cervical collar for a period of one to three weeks. After one year of conservative treatment the patients were assessed using a visual analogue scale. Tapping and compression of the median nerve at the wrist were carried out to elicit referred pain in the shoulder and neck. A local anaesthetic test was performed by infiltrating 0.5% bupivicaine around the median nerve at the most tender site, usually 2.5 cm proximal to the distal wrist crease, which caused temporary resolution of pain in the shoulder and neck. All patients had plain radiography and six had MRI of the cervical spine.
An independent clinician (RW) carried out these assessments.
Of the 27 patients (71%) who had electromyography (EMG) and nerve-conduction studies, all had normal results. The effects of pain on their daily activities were recorded.
Determination of SP and CGRP. Approval of the Ethical Committee was obtained. In the 38 patients blood was taken before operation, and at 13 days and six weeks after surgery. None had heart disease or hypertension. A control group for this part of the study consisted of healthy subjects with no injuries and were randomly chosen by age and gender.
Plasma obtained from centrifuged blood (5 ml) collected in EDTA aprotinin tubes was stored at -80 deg C. Commercially available enzyme-immunoassay kits (Peninsula Laboratories, Merseyside, UK) were used to measure the plasma SP (EIA 7451) and CGRP (EIA 6012). The lowest detectable concentration for plasma CGRP was 0.04 ng/l, and there was no cross-reaction with SP, vasoactive intestinal polypeptide or calcitonin. The lowest detectable concentration for SP was 0.03 ng/l^sup 3^ and there was no cross-reaction with neurokinin (A, B) or neuropeptide K.
To obtain standard curves, known amounts of peptides were incubated with their specific antibodies. Biotinylatedlabelled peptide, added as a tracer, formed immobilised primary antibody/biotinylated-labelled peptide complexes.
The complexes were then allowed to bind to streptavidinconjugated horseradish peroxidases. Any excess biotinylated-labelled peptides and peroxidases were washed away.
Tetramethyl benzidine dihydrochloride, when reacted with conjugated horseradish peroxidases, produces a colour intensity (absorbance) that can be read at 450 nm and from which a standard curve can be derived. The intra- and interassay coefficients of variation were 6.3% and 7.2% for CGRP and 12.4% and 8.3% for SP, respectively.
Statistical analysis. The results were expressed as the mean, median and standard deviation. The non-parametric Mann-Whitney U test was used throughout. A p value of 0.05 was the criterion for statistical significance.
Levels of neurotransmitters. In the patients the mean plasma concentration of SP (220+/- 161 ng/1) before operation was significantly higher (p
Testing of muscle power was performed according to the MRC grading. There was weakness of the pronator teres, the thenar muscles, and the long flexors of the index and middle fingers, which are all innervated by the median nerve. The power of these muscles was between grade 2+ and grade 4. This returned to normal (grade 5) in 36 patients (95%) after operation. Muscle power ranged from grade 3+ to grade 4 for 28 of the control patients (93%). The muscles supplied by the axillary, musculocutaneous, ulnar and radial nerves had grade-5 power.
The Jamar dynamometer was used to compare the grip strength on the affected with the normal side. Table II gives the results.
Before operation paraesthesiae were referred distally into the fingers in 36 patients on tapping over the median nerve 2.5 cm proximal to the wrist crease on the affected side.
This recovered in 33 (87%) after surgery. There was proximal referral of paraesthesiae in 35 patients (92%) and this disappeared in 34 (89%) after operation.
Direct pressure applied for five seconds over the median nerve 2.5 cm proximal to the distal wrist crease produced pain which was referred proximally to the neck, shoulder or the interscapular region in 34 patients (89%). This disappeared in 33 patients after operation (87%). The Floyd nerve-tension test 11 in the upper limb was positive in all patients before surgery, and became negative in 34 (89%) after operation. The test was positive in 28 of the patients treated conservatively (93%). The neck and shoulder pain resolved in 36 patients (95%) after operation.
At follow-up at two years only two of the control group had improvement of their neurological symptoms. The remaining 28 (93%) continued to experience these problems and had chronic pain in the shoulder and neck. There was no recurrence of pain or other symptoms in the surgically-treated group at the end of follow-up.
There was no evidence of fracture or dislocation on radiographs. Ten patients (27%) showed loss of cervical lordosis. Three had narrowing of the disc space at the C4/5 levels with no arthritis of the facet joints. Six patients had MRI of the cervical spine which showed no abnormality.
The visual pain analogue scale showed the subjective assessment of pain before (Fig. la) and after (Fig. lb) surgery. The activities of daily living improved considerably after surgery because of relief from pain (Fig. 2).
Chronic pain in the shoulder and neck is common after a whiplash injury. The cause of the neurological symptoms remains uncertain in the presence of normal neurophysiological investigations and findings on imaging of the neck and shoulder. These symptoms are not typical of radicular pain and, although some are similar to those of the carpal tunnel syndrome, pain in the shoulder and neck pain is not characteristic of entrapment of the median nerve at the wrist. In our study, 27 patients (71%) had a normal EMG.
Alpar5 reported that of 225 patients with whiplash injury only 3% had abnormal EMG changes. Ide et al6 also found normal neurophysiological investigations in patients with symptoms and signs of irritation of the brachial plexus and entrapment of peripheral nerves after a whiplash injury. We feel that in a whiplash injury the median nerve may be injured by stretching of the neck due to the extension, flexion and vertical components of the force.
The characteristic features of atypical carpal tunnel syndrome are referral of dysaesthesia to the shoulder and neck on tapping over the median nerve proximal to the wrist, increase in pain in the shoulder and neck by direct pressure on the same area and disappearance or improvement of the shoulder and neck pain on infiltration of this site with 6 ml of 0.5% bupivicaine. These features suggest that chronic shoulder and neck pain after whiplash injury may arise from the median nerve at the level of the wrist and that the pain is referred proximally. The nerve pain is thus not felt at the site of its origin 12 It has been shown that pain from the median nerve may be experienced in the neck and shoulder.13
The EMG and nerve-conduction studies are normal because most of the fibres which constitute a peripheral nerve are A-delta fibres of small diameter and unmyelinated C fibres. Standard nerve-conduction studies assess function in the large and myelinated fibres and thus only test a few of those which constitute a peripheral nerve.
Such studies are therefore unsuitable as an aid in the diagnosis of this condition,la.ls There is evidence that neurotransmitters such as SP and CGRP are released in the dorsal horn with other agents which sensitise nociceptors.
When impulses arrive from C-fibre afferents, SP is released 16 and the plasma levels of neurotransmitter peptides are elevated 10
Our patients with an isolated whiplash injury had high plasma levels of pain neurotransmitters which fell to normal levels after decompression of the median nerve at the wrist. The plasma levels of SP are also raised in other painful conditions,17-20 and those of CGRP are altered in soft-tissue injuries21, in chronic pain22 and infection23.
Carpal tunnel decompression is indicated in patients who have chronic neck,shoulder and arm pain after a whiplas injury. Changes in the plasma levels of neurotransmitter peptides and independent clinical and function outcomes confirm the benefits of this treatment. The relief from pain and restoration of normal muscle power are evidence that any decrease in muscle power is due to inhibition of pain.
Jamar dynanometric studies may not be helpful in the assessment of individual muscle weakness. The presence of a normal EMG and nerve-conduction studies should not deter surgeons from offering carpal tunnel decompression to patients with chronic pain in the shoulder and neck after a whiplash injury.
No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
1. McNabI The “Whiplash Syndrome”. Orthop Clin North Am 1971;2:389-403.
2. Parmar HV, Raymakers R. Neck injuries from rear impact road accidents: a long-term clinical and radiological review. Injury 1993;24:79-82.
3. Radanov B, Sturzenegger M, Distefano G. Long-term outcome after whiplash injury: a two-year follow-up considering features of accident mechanism, and somatic, radiological and psychological findings. Medicine (Baltimore) 1995;74:281-97.
4. Hohl, M. Soft tissue injuries of the neck in automobile accidents. J Bone and Joint Surg [Am] 1974;56-A: 1675-82.
5. Alpar, EK. ‘Whiplash’ injury and median nerve entrapment. Injury 1997;28:243.
6. Ide M, Ide J, Yamaga M, Takagi K. Symptoms and signs of irritation of the brachial plexus in whiplash injuries. J Bone Joint Surg [BrI 2001;83-B:226-9.
7. Bogduk N, Yoganandan N. Biomechanics of the cervical spine Part 3: minor injuries. Clin Biomech 2001;16:267-75.
8. Jonsson H Jr, Cesarini K, Sahlstedt B, Rauschning W. Findings and outcome in whiplash-type neck distortions. Spine 1994;19:2733-43.
9. Brain SD, Williams TJ. Interaction between the tachykinins and calcitonin gene related peptide lead to the modulation of oedema formation and blood flow in rat skin. Br J Pharmacol 1989;97:82.
10. Yaksh TL, Jessell TM, Gamse R, Mudge AW, Leeman SE. Intrathecal morphine inhibits substance P release from mammaliam spinal cord in vivo. Nature 1980;286:155-7.
11. Floyd WE Jr. Nerve compression. In: Kasdan ML, Amadio PC, Bowers WH, eds. Technical tips for hand surgery. Philadelphia: Mosby 1994;163.
12. Devor M, Seltzer Z. Pathophysiology of damaged nerves in relation to chronic pain. In: Wall PD, Melzack R, eds. Textbook of pain. 4th edition. Edinburgh, etc. Churchill Livingstone 1999;129-55.
13. Inman VT, Saunders JB. Referred pain from skeletal structures. J New and Ment Dis 1944;99:660-7.
14. Buchthal F, Rosenfalck A, Behse F. Sensory potentials in normal and diseased nerves. In: Dyck PJ, Thomas PK, Lambert EH, Bunge R, eds. Peripheral neuropathy. Vol. 1. 2nd edn. Philadelphia, etc: W B Saunders 1984;981-1015.
15. Buchthal F, Rosenflack A, Trojaborg W. Electrophysiological findings in entrapment of the median nerve at wrist and elbow. J Neurol Neurosurg Psychiat 1974;34:340.
16. Dickenson AH. Spinal cord pharmacology of pain. Br J Anaesth 1995;75:193-200.
17. Michaels LA, Ohene-Frempong K, Zhao H, Douglas SD. Serum levels of substance P are elevated in patients with sickle cell disease and increase further during vaso-occlusive crisis. Blood 1998;92:3148-51.
18. Cohen RH, Perl ER. Contributions of arachnidonic acid derivatives and substance P to the sensitisation of cutaneous nociceptors. J Neurophysiol 1990;64:457-64.
19. Gotoh M, Hamada K, Yamakawa H, Inoue A, Fukuda H. Increased substance P in subacromial bursa and shoulder pain in rotator cuff diseases. J Orthop Res 1998;16:618-21.
20. Yamashita T, Ishii S, Usui M. Pain relief after nerve resection for post-traumatic neuralgia. J Bone Joint Surg (Br] 1998;80-B:499503.
21. Onuoha GN, Alpar EK. Calcitonin gene-related peptide and other neuropeptides in the plasma of patients with soft tissue injury. Life Sci 1999;65:1351-8.
22. Borici-Mazi R, Kouridakis S, Kontou-Fili K. Cutaneous responses to substance P and calcitonin gene-related peptide in chronic urticaria: the effect of cetirizine and dimethindene. Allergy 1999;54:46-56.
23. Norlander T, Nilsson L, Rivero C, et al. Effects of experimental Myocoplasma pulmonis infection on sensory neuropeptides and airway mucosa in the rat. Eur Respir J 1997;10:2334-42.
Emin K. Alpar, Gracey Onuoha, Vijay V. Killampalli, Ruth Waters From the University Hospital Selly Oak NHS Trust, Birmingham, England
E. K. Alpar, MCh Orth, FRCS Ed Orth, Consultant Trauma and Orthopaedic Surgeon
G. Onuoha, PhD, Research Fellow
V. V. Killampalli, DNB Orth, MSc Traumatology, Clinical Research Fellow
R. Waters, FRCS (Plast), Consultant Plastic Surgeon
Department of Trauma and Orthopaedic Surgery, University Hospital Selly Oak NHS Trust, Raddlebarn Road, Birmingham B29 6JD, UK.
Correspondence should be sent to Mr E. K. Alpar at 18 Amesbury Road, Moseley, Birmingham B 13 8LD, UK.
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