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Managing chronic non-malignant pain

Kiran Koneti, Sam Eldabe and Ashish Gulve
29 May, 2014  
Development of multi-contact lead, peripheral nerve field stimulation for the treatment of long-term, non-malignant pain is discussed
 
Kiran Koneti MBBS DA FCARCSI FRCA EDRA
Consultant in Anaesthesia and Pain,
Northern Deanery,
Newcastle upon Tyne, UK
Sam Eldabe MBBS FRCA FFPMRCA 
Consultant in Pain Management and Anaesthesia,
The James Cook University Hospital, Middlesbrough,
UK; President,
Neuromodulation Society of UK and Ireland
Ashish Gulve MBBS FCARCSI DPMed FFPMCAI 
Consultant in Pain Management and Anaesthesia,
The James Cook University Hospital, Middlesbrough, UK
 
The use of electrical stimulation for the treatment of pain was pioneered by Scribonius Largus, physician to the Roman emperor, Claudius, where he used torpedo fish and electric eels to treat migraine. After the discovery of electricity, it was used in late 1800s by application of alternating current electrotherapy to peripheral nerves by Julian Althaus.(1) It was not popular, however, until after 1967, when it was trialled for use as spinal cord stimulation (SCS) in chronic pain by Shealy et al.(2)
 
Neuromodulation involves the selective application of a programmable pulse waveform through a series of electrodes within leads to stimulate afferent nerve fibres and subsequently reduce the perception of pain.(1) Since the initial use of SCS in chronic pain, new approaches have been developed to target more selectively areas of pain and provide more efficient paraesthesia coverage, and the list of indications for neuromodulation has continued to grow.
 
Direct stimulation of peripheral nerves, requiring open surgical dissection and placement of electrodes proximal to the painful segment of the exposed peripheral nerve, has had mixed results.(3) With the drive from innovative physicians, along with the technological advancement in terms of the development of the multi-contact lead, peripheral nerve field stimulation (PNFS) came to existence. 
 
In PNFS, leads are placed percutaneously and advanced under the skin in the area of pain, allowing regional field stimulation without the need for the manipulation of the epidural space and more invasive surgical placement required for direct peripheral nerve stimulation or SCS. In PNFS, leads stimulate the region of the affected nerves or the dermatomal distribution of these nerves, which then converge back on the spinal cord. 
 
Pathophysiology and mechanism of action
The exact pathophysiology and mechanism of action of PNFS in low back and other peripheral pain are not clear. However, similar to the postulated mechanism for percutaneous electrical nerve stimulation (PENS),(4) neurostimulation in subcutaneous tissues with PNFS may alter local blood flow, block cell membrane depolarisation and axonal conduction and affect neurotransmitters, and thereby similarly block or jam nociceptive input back at the spinal neurons. As postulated for PENS and transcutaneous electrical nerve stimulation,(4) PNFS may cause an increase in endogenous endorphins and other opiate-like substances, normalise nerve conduction velocity and decrease conduction latency and the mechanical pain threshold. PNFS may also relieve abdominal visceral pain by modulating cutaneous nerves in the dermatomal distribution of the viscerotome involved in pain.(5)
 
Indications
Chronic pain refractory to systemic medical therapies has a significant impact on patients’ quality of life. PNFS has been emerging as a promising treatment option for a growing list of chronic pain conditions in craniofacial, thoracic, abdominal, low back and pelvic regions.(6–8) Evidence supporting the use of PFNS comes from various published case series. There is no clear consensus on definitive indications.
 
Selection criteria for PNFS trial
  1. A clearly defined, discrete focal area of pain, with a neuropathic or combined somatic neuropathic pain component with characteristics of burning and increased sensitivity.
  2. Failure to respond to other conservative treatments, including medications, psychological therapies, physical therapies, surgery and pain-management programmes.
  3. Psychological clearance (including a psychologist ruling out major drug addictions or significant psychiatric disorders that might impact on successful treatment).
  4. Informed consent.
 
Craniofacial pain
PNFS of the occipital nerve has been used successfully in occipital neuralgias, cluster headache, migraines and other refractory headaches, craniofacial pain, fibromyalgia and post-herpetic neuralgia.(9) There are a number of randomised studies(10,11) looking at the occipital nerve field stimulation for migraine. 
 
Low back pain
SCS was primarily used for radicular lower limb pain and, to some extent, back pain, particularly following failed back surgery syndrome (FBSS). Unfortunately, SCS stimulation failed to cover adequately the axial back pain. PNFS has shown to be effective in back pain of FBSS in a limited number of cases.
 
Abdominal pain
PNFS was used in chronic pancreatitis, abdominal pains refractory to medical management and other conditions.
 
Inguinal and pelvic pain
PNFS has been effective in chronic post-surgical pain in the inguinal and pelvic areas in some case series.
 
Exclusion criteria
To facilitate appropriate patient selection, the multidisciplinary team assessment needs to consider some of the 
following factors:
  • Pathophysiologic contraindication.
  • Coexisting conditions, for example, sepsis and coagulopathy.
  • Coexisting deteriorating neurological condition.
  • Patients non-compliant with medical therapy.
  • Unresolved psychiatric illness.
  • Unresolved issues of secondary gain.
  • Abnormal pain behaviour.
Methods
After appropriate patient selection, most patients undergo a trial period of a few days’ duration, although it is variable across institutions. Certain headaches can take a few weeks/months to respond and a trial is not possible. The successful trial is defined by a reduction of at least 50% of the original pain, with the stimulation covering most of the painful region, a reduction in reliance on analgesics and improvement in quality of life.
 
PNFS trial
The trial procedures are performed in sterile operating theatres with or without sedation. The area of pain is clearly marked before the start of procedure on clinical assessment. The leads are placed under fluoroscopic guidance with local anaesthetic using a wide bore Tuohy needle according to the supplier. Depending on the site and area of pain, between one and four leads may be used. Stimulation is performed on table to ensure paraesthesia is felt in the area of pain and it is comfortable. The leads are sutured to the skin and sterile dressings applied. While patients are monitored in recovery, initial stimulation parameters are programmed, followed by attachment of the external power source to the leads during the trial period.
 
PNFS implantation procedure
After the successful trial period, patients are selected for permanent implantation procedure (Fig 1). The position of the successful trial leads and placement of the implantable pulse generator (IPG) are marked. The leads are replaced as in the trial procedure, sutured to the deep fascia and tunnelled to the site of the IPG, which is placed in a tight pocket created by blunt dissection. The site of the IPG depends on the site of leads and some common sites are upper buttock, upper chest and abdominal wall. The leads are connected to the IPG and secured after impedance is verified. Further refinement of stimulation parameters is performed over the following weeks. 
 
Current evidence
Even though PNFS has been in practice for a few years, it was mainly used in certain groups of patient and many case series were produced with small numbers. There are only two large case series published to date. The nationwide, multicentre, retrospective study from Austria by Sator-Katzenschlager et al(12) involved 111 patients with various chronic non-malignant pain conditions. This study showed that the mean pain intensity improved by more than 50% (mean numerical rating scale (NRS) reduced from 8.2 to 4.0) with p=0.000912 in three months after PNFS implantation. The other large prospective, observational study from Australia by Verrills et al(9) involved 100 patients with PNFS for the treatment of various chronic pain conditions. This study demonstrated an average pain reduction of 3.2 ± 2.3 NRS points (4.2 ± 2.5 from 7.4 ± 1.7) with p≤0.00 during a follow-up period of 8.1 ±  4.7 months along with a reduction of analgesic use in 72% of patients following PNFS.(9) 
 
Advantages
PNFS has several advantages over SCS in chronic pain treatments, as it does not carry the same neurological risks, such as epidural haemorrhage, paralysis and infections – meningitis, epidural abscesses. In view of minimal invasiveness, the main advantages include: reversibility, low morbidity with fewer side effects, minimally invasive implantation, percutaneous lead placement, lead insertion with the patient awake to confirm proper lead placement, and programmable stimulator systems to improve coverage and effectiveness 
of stimulation.(13)
 
Complications
PNFS is a relatively safe and well-tolerated technique for controlling intractable pain and does not lead to the serious complications of SCS. The common events that are reported are infection, lack or inadequate pain relief, lead erosions, lead migration, lead dislocation/fracture and hardware failure. The two large studies on PNFS showed a complication rate of 24%(12) and 16%(9) compared with a complication rate of 45% for SCS (Table 1).(14)
 
Conclusions
PNFS is an emerging neuromodulation technique. It appears to be  safe and simple, avoiding the potential complications associated with manipulation of the epidural space. Current experience, however, remains limited to two large case series and a number of smaller case series, where the potential for bias in the reporting of the results and complications cannot be eliminated. Furthermore, most available studies have a short duration of follow up. Therefore, what is needed to consolidate the role of this technique in current neuromodulation practice is a randomised, controlled trial with adequate duration of follow up, comparing PNFS to the current gold standard in therapy. In the long-term, more case series will help to narrow the field of indications to the most appropriate candidates for the therapy. 
 
References
  1. Keller T, Krames ES. On the shoulders of giants: A history of the understandings of pain, leading to the understandings of neuromodulation. Neuromodulation 2009;12(2):77–84.
  2. Shealy CN et al. Electrical inhibition of pain by stimulation of the dorsal columns: preliminary clinical report. Anesth Analg 1967; 46:489–91.
  3. Alo KM, Holsheimer J. New trends in neuromodulation for the management of neuropathic pain. Neurosurgery 2002;50(4):690–704.
  4. Hamza MA et al. Percutaneous electrical nerve stimulation: A novel analgesic therapy for diabetic neuropathic pain. Diabetes Care 2000;23:365–70.
  5. Khan YN, Raza SS, Khan AE. Application of spinal cord stimulation for the treatment of abdominal visceral pain syndromes: Case reports. Neuromodulation 2005;8(1):14–27.
  6. Oh MY et al. Peripheral nerve stimulation for the treatment of occipital neuralgia and transformed migraine using a C1-2-3 subcutaneous paddle style electrode: A technical report. Neuromodulation 2004;7(2):103–12.
  7. Slavin KV, Wess C. Trigeminal branch stimulation for intractable neuropathic pain: Technical note. Neuromodulation 2005;8(1):7–13.
  8. Johnstone CS, Sunderaj R. Occipital nerve stimulation for the treatment of occipital neuralgia – Eight case studies. Neuromodulation 2006;9(1):41–7.
  9. Verrills P et al. Peripheral nerve field stimulation for chronic pain: 100 cases and review of the literature. Pain Med 2011;12(9):1395–405.
  10. Paemeleire K et al. Phenotype of patients responsive to occipital nerve stimulation for refractory head pain. Cephalalgia 2010;30(6):662–73.
  11. Saper JR et al. Occipital nerve stimulation for the treatment of intractable chronic migraine headache: ONSTIM feasibility study. Cephalalgia 2011;31(3):271–85.
  12. Sator-Katzenschlager S et al. Subcutaneous target stimulation (STS) in chronic non cancer pain: a nationwide retrospective study. Pain Practice 2010;10(4):279–86.
  13. North RB. Spinal cord and peripheral nerve stimulation: Technical aspects. In Simpson BA (ed). Pain Research and Clinical Management. Electrical Stimulation and the Relief of Pain. Elsevier, 2003;15(Chapter 12):183–96.
  14. Kumar K et al. Spinal cord stimulation versus conventional medical management for neuropathic pain: a multicentre randomised controlled trial in patients with failed back surgery syndrome. Pain 2007;132(1–2):179–88.