Friday, September 2, 2011

PENS for Superficial Neuropathic Pain Tested

Neuropathic Pain A well-designed but small study of PENS (percutaneous electrical nerve stimulation) for superficial, chronic nerve-related pain found that the modality was effective in providing short-term relief. However, while this approach may be promising for certain manifestations of neuropathic pain, the many limitations of this trial and needs for further research should be taken into account.

PENS is an interventional electrical neuromodulation technique that has demonstrated some therapeutic potential in various chronic pain conditions during recent years, but well-blinded controlled studies of this modality have been lacking, according to a research team from the UK. Therefore, Jon H. Raphael, MD, and colleagues conducted a randomized, double-blind, sham-controlled, crossover trial in 31 patients experiencing chronic pain with surface hyperalgesia to investigate the efficacy of PENS [Raphael et al. 2011].

Writing in an early online edition of the journal Pain Medicine, the researchers note active treatment consisted of probes inserted through the skin into the area of primary superficial pain followed by administration of electrical stimulation — alternating between 2 Hz and 100 Hz every 3 minutes — for 25 minutes. Sham therapy followed identical procedures but without any electrical current applied. Responses were assessed immediately after treatment via a subjective 0-to-10 numeric pain-rating scale (NRS) and an objective measure of pain pressure threshold (PPT, using von Frey aesthesiometer).

Active PENS therapy significantly reduced median NRS scores by 7 points compared with sham/placebo (there was no median-score change at all in the sham group). At the same time, PENS therapy favorably increased the PPT — the subject’s ability to tolerate pressure on the painful area — by 3-fold on average. There also was a statistically significant difference (P < 0.0001) between mean (±SD) changes in NRS for the active (3.9 ±3.2) compared with the sham (0.1 ±0.4) therapy, as well as significant differences (P = 0.007) between changes in PPT for the active versus sham therapy. These differences also were of apparent clinical importance in affording pain relief with PENS.

The authors conclude that PENS therapy appears to be effective in providing short-term pain relief in chronic pain conditions. However, this was a small study and the durability of beneficial effects from PENS was unmeasured, so the researchers recommend further studies, involving larger sample sizes and longer follow-up. There also were other limitations that should be taken into account.

COMMENTARY: The researchers describe this as a “proof of concept” study, which might be interpreted as a justification for the low number of subjects and methodological shortcomings. They note that a sample size of 30 patients in a cross-over design was determined to provide sufficient statistical power for valid analyses, but they do not provide specific data on effect sizes or other parameters that went into the power calculations.

Besides the small number of subjects, they also enrolled a very heterogenous group that detracts from the external validity of outcomes. Ages of patients ranged from 23-84 years (mean 56 years) and they had suffered from chronic pain from 1 to 35 years (mean 8.1 years); 58% were female. Superficial-pain diagnoses varied broadly, including surgical scar pain, occipital neuralgia, posttraumatic neuropathic pain, stump pain, inflammatory neuropathic pain, chronic low back pain, complex regional pain syndrome, pain following total knee replacement surgery, chronic cervical pain, and post-herpetic neuralgia. This diversity also prevented any subgroup analyses to determine PENS benefits in one condition versus another.

Subjects had previously received a wide spectrum of therapies for their chronic pain, that had been either ineffective or of limited benefit. These included pharmacotherapies of various types, steroid/nerve block injections, lidocaine patches, TENS therapy, acupuncture, physiotherapy, hypnotherapy, chiropractic or osteopathic therapy, and herbal remedies.

Of interest, in the cross-over design of this study, although patients had a 4-week ‘wash out’ period before being switched to the alternate condition (sham or active treatment), the patient blinding was negated in the second arm of the study. This was because there was a telltale tingling sensation associated with active PENS; so, at the second treatment subjects knew if they were receiving a real or fake therapy, as compared with what they received initially. However, examining data from only treatment na├»ve subjects during the initial arm of the trial, the authors found there were still statistically and clinically significant improvements in NRS and PPT measures afforded by PENS.

PENS is not an entirely new modality but the research on it thus far has been limited. It is an interventional approach somewhat related in concept to acupuncture and TENS, as described by Raphael et al. in their study discussion:

  • In acupuncture, needles are inserted intradermally or into muscle according to Traditional Chinese Medicine (TCM) points and meridians, or following a dermatomal distribution. The needles themselves act as a mechanical stimulation agent, but at times, a low-frequency electrical stimulus is applied. At low-frequency (2 Hz), analgesic effects are induced via mu- and delta-opioid receptors, and at a high-frequency stimulus (100 Hz) by activating kappa-opioid receptors, the authors note.

  • TENS, or Transcutaneous Electrical Nerve Stimulation, involves applied electrical stimulation to the skin surface, with both high (50–100 Hz) and low (2 Hz) frequencies used and each is thought to work by different mechanisms. High-frequency TENS is believed to selectively activate large diameter afferent nerves to reduce nociceptor cell activity and sensitization at a segmental level in the central nervous system. Low-frequency TENS can activate small diameter motor afferent pathways to elicit extra-segmental analgesia. However, TENS cannot deliver both high and low frequencies within a short timeframe as with PENS, which provides for a rapidly alternating frequency of 2 and 100 Hz at 3-second intervals and, therefore, may offer combined benefits of both frequency ranges, according to Raphael and colleagues.

  • In the case of PENS, the authors continue, needle-like probes are inserted percutaneously (through and below the skin surface) based on anatomical and physiological considerations. The probes act as mere vehicles to deliver the electrical stimulus through the skin, bringing it into close proximity with the peripheral nerves. The physical insertion of the probes themselves is not believed to have any pain-relieving effect, as with acupuncture. PENS probes can be introduced into areas that are slightly outside of where the skin is most sensitive, thus aiding compliance in patients intolerant of TENS due to allodynia. A further advantage of percutaneous probe insertion is that it bypasses skin resistance to deliver the full magnitude of the electrical stimulus and in closer proximity to the stimulated peripheral nerve(s).

In the present study of PENS by Raphael et al. only 3 subjects had previously tried TENS therapy and 7 had used acupuncture, all unsuccessfully. However, comparisons between the three modalities could not be made based on data collected for this study.

The randomization and blinding procedures applied in this present study seem adequate, and the sham/placebo condition used for comparison with active PENS therapy appeared to be valid, provided patients are not crossed-over from one to the other. Apparently, the researchers were not expecting long-term effects of PENS therapy, since only 1-month was determined as a suitable wash-out period for any initial benefits from the first arm of the study to wane.

However, a concerning aspect of this study is that, while PENS might be of some value in providing immediate pain relief for a variety of neuropathies that manifest as superficial pain (hyperalgesia), the durability of these effects is still unknown. Until longer-term efficacy can be established in much larger groups of patients with chronic neuropathic pain the importance of PENS for clinical practice remains to be determined.

REFERENCE: Raphael JH, Raheem TA, Southall JL, et al. Randomized Double-Blind Sham-Controlled Crossover Study of Short-Term Effect of Percutaneous Electrical Nerve Stimulation in Neuropathic Pain. Pain Medicine. 2011(Aug), online ahead of print [abstract here].