PAIN MEDICINE Volume 10 • Number 4 • 2009

Pulsed Radiofrequency for Chronic Testicular Pain— A Preliminary Report pme_581

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Saumya Misra, MS, FRCS,* Stephen Ward, FRCA,† and Charles Coker, FRCS (Urol)* Departments of *Urology and †Pain Medicine, Brighton and Sussex University Hospitals Trust, Brighton, UK

ABSTRACT

Objective. To evaluate the effectiveness of pulsed radiofrequency (PRF) of spermatic cord in the treatment of chronic testicular pain.

Results. Ten patients were entered into the study but one was lost to follow-up. Of the nine patients evaluated, four had complete resolution of pain, while one had partial pain relief. Three patients experienced no change and one reported that his pain was worse. All patients who experienced complete and partial pain relief continued to do so at a mean long-term follow-up of 9.6 months (range 3–14 months). There were no complications observed immediately or during the follow-up period. Conclusion. In this pilot study, pain scores improved in five out of nine patients. PRF of spermatic cord appears to be a safe minimally invasive outpatient procedure that should be investigated further with placebo-controlled trials.

Key Words. Chronic Testicular Pain; Pain Score; Pulsed Radiofrequency

Introduction

C

hronic testicular pain is defined as intermittent or constant, unilateral or bilateral testicular pain for ⱖ3 months that significantly interferes with the daily activities of the patient so as to prompt him to seek medical attention [1]. Strebel et al. estimated that about 2.5% of all urology office visits are attributable to chronic testicular pain [2]. This often presents a management dilemma for clinicians, owing to the lack of a standard or an effective treatment. Intrinsic testicular causes involve some degree of nerve trauma to the spermatic cord such as following vasectomy, where there is an increased incidence in patients with

Reprint requests to: Saumya Misra, MS, FRCS, Department of Urology, Princess Royal Hospital, Lewes Road, Haywards Heath, RH16 4EX, UK. Tel: +44-1444-441881; Fax: +440-1444-473494; E-mail: [email protected].

sperm granulomas [3]. Epididymitis and direct trauma to the testis may also lead to chronic testicular pain, a possible mechanism being entrapment of nerves in scar tissue following injury or inflammation [3]. Sources of referred pain include the ureter, back and entrapment neuropathies of the ilioinguinal or genitofemoral nerves, often following inguinal hernia repair [4]. Roughly 25% of cases are considered to be idiopathic [1]. The initial treatment of patients with chronic testicular pain involves a trial of empirical antibiotics, anti-inflammatory analgesics, and sometimes a low dose of antidepressants [5]. The use of alpha receptor blockers to reduce theoretical obstruction or spasm in the vas deferens has been recently advocated [4]. Minimally invasive treatment options include needle aspiration of tense epididymal cysts (where such exist) or local anesthetic infiltration of the spermatic cord, with or

© American Academy of Pain Medicine 1526-2375/09/$15.00/673 673–678

doi:10.1111/j.1526-4637.2009.00581.x

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Design. Ten patients with chronic testicular pain were treated with PRF stimulation of the spermatic cord. A radiofrequency probe placed percutaneously into the spermatic cord was used to deliver four 120-second cycles of 20-millisecond pulses at 2 Hz. Test stimulation was first used to confirm the precise placement of the probe. The short-form McGill Pain Questionnaire was used to assess pain before treatment and at 3 months. Patients who had experienced improvement were followed up by telephone, to determine whether pain relief was sustained.

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Methods

Approval for this prospective uncontrolled pilot study was obtained from the local research ethics committee. All patients had suffered from testicular pain for at least 3 months and had failed conservative treatment. A detailed history was taken and examination performed to identify the possible cause of pain. Prior to inclusion in the study, patients had further investigations where indicated, to exclude the possibility of referred pain. In patients with bilateral pain, the worse side was treated. Patients were initially provided with an information sheet detailing the technique of PRF, the expected effects and possible side effects, and after which written consent was obtained. Using an aseptic technique, a 22 gauge SMK-C10 100 mm cannula (Radionics, Burlington, MA, USA) with a 5 mm active tip was inserted into the spermatic cord at the neck of the scrotum, without local

Figure 1 Radiofrequency probe positioned in the spermatic cord at neck of the scrotum.

anesthetic (see Figure 1). Most patients experienced minor discomfort during needle insertion. The stylet was then removed and the radiofrequency (RF) probe inserted. Sensory stimulation at 50 Hz was undertaken to verify the position of the needle using a stimulation threshold of 0.5 V. The needle was moved in the spermatic cord until concordant pain (pain in the same area of distribution) was described by the patient at less than 0.5 V, indicating proximity to the nerve. PRF was then applied using the RF lesion generator system (model RFG-3C, Radionics), using the following settings: 2-Hz frequency, 20-ms pulse, and 120-s cycles for a total of 8 minutes, based on the protocol developed in our pain clinic. The output voltage was adjusted for the temperature so as not to exceed 42°C. Impedance ranged from 240 to 700 ohms. All patients were reviewed after 3 months to assess efficacy and side effects. The short-form McGill Pain Questionnaire [11], which includes a 10-point (0 = no pain to 10 = worst pain) visual analog scale (VAS), was used to evaluate pain before and 3 months after treatment. Patients, who reported pain relief after PRF, were telephoned 8–14 months after the procedure to ascertain whether pain relief was sustained. Results

Ten patients underwent PRF treatment between September 2005 and December 2006. One patient was not contactable for follow-up and was excluded from analysis. The mean age was 49 years (standard deviation = 10, range 32–65) and the

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without methylprednisolone [4]. Pain relief from such nerve blocks is invariably transient. Local anesthetic infiltration of the pelvic plexus under transrectal ultrasound guidance and transcutaneous nerve stimulation (TENS) have also been tried with varied success [1,6]. Neurectomy has been advocated to treat trapped nerves after surgery but this may be followed by neuroma formation that can produce ectopic discharges and lead to worsening symptoms [7]. Other surgical procedures for patients who fail to respond to conservative measures include epididymectomy [8], vasovasostomy [9], orchidectomy [1], and microsurgical dennervation of the spermatic cord [3]. Surgery, however, should only be used as a last resort as its effect is potentially irreversible and cure is never guaranteed. The use of pulsed radiofrequency (PRF), where a high-frequency current is applied in bursts of 20 ms with a silent time of 480 ms, allowing elimination of heat, has generated increasing interest of pain physicians for the management of various pain syndromes [10]. Cohen and Foster [7] reported complete pain relief at 6 months in three patients with chronic testicular and inguinal pain of varied etiology treated with PRF. Encouraged by this preliminary report, we conducted a pilot study to evaluate the effectiveness of PRF applied to the spermatic cord for treating refractory chronic testicular pain in a series of consecutive patients, which to our knowledge is the first evidence of benefit.

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Pulsed Radiofrequency of Spermatic Cord Table 1

Patient characteristics, previous treatment, and outcome of pulsed radiofrequency treatment

Patient No.

Age (Years)

Duration of Pain (Months) and Laterality

1

44

66 Bilateral

2

41

12 Bilateral

3

53

4

44

5

32

24 Unilateral 54 Unilateral 120

Past Medical History

Previous Nerve Blocks

Outcome

Epididymitis Anxiety Depression Vasectomy Back pain Lower urinary symptoms Epididymitis Diabetes None

Transcutaneous nerve stimulation, ilioinguinal nerve block—no benefit None

No change

Ilioinguinal nerve block—worse

No change

None

Significantly better

None

Obturator nerve block Ilioinguinal nerve block Injection of pubic tubercle—temporary relief None

Partially better

None

Worse

Ilioinguinal and genitofemoral nerve block—50% relief None

Significantly better

Unilateral 62

12

7

52

Unilateral 6

8

65

9

48

Unilateral 36 Unilateral 180 Bilateral

History of undescended testis as a child Hemospermia Previous surgery for testicular pain Back pain Bilateral hernia repair Vasectomy Trauma 20 years ago Back pain

median duration of pain was 36 months (range 6–120). All nine patients had tried and failed conservative treatment with antibiotics and nonsteroidal anti-inflammatory analgesics. One patient had taken antidepressants and another had tried gabapentin without any effect. None were on opioids. In addition, four patients had previously had TENS and various nerve blocks (See Table 1) but had not obtained any significant relief. One patient had unilateral groin pain following bilateral hernia repair, which responded partially to an ilioinguinal nerve block. He developed chronic testicular pain following this, at which time he was entered in our study. One patient had recurrent pain following temporary relief after scrotal exploration, freeing of adhesions, and orchidopexy. Other etiologies are listed in Table 1. On examination, all patients had testicular and/or epididymal tenderness and one patient had a palpable unilateral grade II varicocoele. This was not felt to be the cause of his pain, which was bilateral. Diagnostic ultrasound detected varicocoeles in three more patients, but these were not clinically relevant. Further urological investigations where indicated did not reveal any abnormalities. Most patients described pain in the testicle, while one patient described pain in the area of superficial inguinal ring. “Aching” was the commonest (8 out of 9 patients), while “shooting” and

Significantly better

Significantly better

“gnawing” were the least common sensory descriptors used for testicular pain. Five out of nine patients used “sickening” to describe the affective quality. Median VAS scores decreased from 7.1 (range 4.3–8.7) before treatment to 4.2 (range 0–8.6) 3 months after treatment (See Table 2). Four patients (cases 4, 6, 8, and 9) described near complete pain relief. Their VAS and total pain rating index scores improved by 79–100% and 75–100%, respectively. One patient reported partial relief with the VAS score decreasing by 44%. Three patients were unaffected. One reported that he was significantly worse after the procedure. He was a very anxious gentleman, had a very high affective score postprocedure, and all his pain rating indices and VAS scores had increased. He subsequently underwent an orchidectomy elsewhere. Where improvement occurred, a perceptible difference was noticed within 2 weeks in most

Table 2 Pain scores before and 3 months after treatment (median, range) N = 9 Pain Score

Before Treatment

After Treatment

Sensory pain rating index Affective pain rating index Total pain rating index Visual analog scale Overall intensity

11 2 17 7.1 3

5 2 7 4.2 2

(4–23) (0–9) (4–29) (4.3–8.7) (2–5)

(0–22) (0–6) (0–27) (0–8.6) (0–5)

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6

No change

676 cases. Pain relief in all five patients was sustained (mean follow-up period 9.6 months, range 3–14 months). They were all able to resume normal activities. One patient reported some recurrence of pain on the same side a year after treatment, but the pain was much less intense, his quality of life was much improved, and he declined further treatment. There were no side effects or procedurerelated complications. Discussion

genital branch of genitofemoral nerve that ascends along with the other cord structures and are easily accessible at the neck of the scrotum. From our experience, we had found that some of our patients had persistent testicular pain despite relief of inguinal pain with ilioinguinal and iliohypogastric nerve blocks. Injecting local anesthetic into the spermatic cord (where it emerges out of the superficial inguinal ring medial to the pubic tubercle) to block the above-mentioned nerves is an accepted method of producing local anesthesia for scrotal procedures [16]. Using the same principle, we positioned the RF probe at the neck of the scrotum to increase the chances of stimulating most pain-carrying afferent fibers from the testicle. In our study, four out of nine patients had complete resolution and one had partial pain relief. It is not clear why some patients improved markedly while others remained unaffected. The wide range of impedance values might suggest variability in needle position, but all the patients had responded to test stimulation at less than 0.5 V and continued to feel the pulsing throughout the procedure. The best results were obtained in patients with isolated testicular pain who did not appear to have significant psychological problems, although the latter aspect was not formally evaluated. However, our sample size was too small to make any meaningful recommendations about other parameters that might predict a better outcome. A larger study, with patients stratified according to etiology, might be able to shed more light on the suitability of PRF for treating testicular pain of different etiologies, targeting different points in the pain pathway. Conducting randomized placebo-controlled trials in interventional pain management has methodological and ethical limitations [10]. We accept that the number of patients in this study are too small to draw definite conclusions, but the results are encouraging to us. Absence of a control arm is a drawback, but the study was conceived as a pilot to test the effectiveness of PRF to treat chronic testicular pain. Therefore, a placebo effect cannot be ruled out. Natural resolution of symptoms seems extremely unlikely, as most patients had endured long periods of pain before having treatment. We found pain relief to be sustained at a mean follow-up of 9.6 months. Longer follow-up data are needed to confirm long-term efficacy. However, the procedure is safe and could be repeated if there was recurrence of pain. We excluded patients with the possibility of referred

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In our case series, we found that PRF provided significant pain relief in four out of nine patients with chronic testicular pain of varied etiology, and the pain relief was sustained. To our knowledge, this is the first study evaluating the effect of PRF on the spermatic cord, in a group of patients with this chronic condition. PRF has been investigated as a potentially less destructive alternative to RF thermal neurolytic destruction in the management of various chronic pain syndromes [10]. The method seems to work irrespective of the site of exposure of the neuron to PRF [12]. While PRF is admittedly safer than conventional RF and effective when applied to the dorsal root ganglia (DRG) for treatment of radicular pain [13], peripheral nerves have also been treated successfully [10]. Cohen and Foster [7] reported on the use of PRF to treat inguinal and scrotal pain in three patients. They performed PRF procedures on three different peripheral nerves—ilioinguinal, iliohypogastric, and genital branch of genitofemoral—and these showed excellent pain relief at 6 months. Rozen and Parvez [14] treated five patients with ilioinguinal neuralgia secondary to hernia repair with PRF of T12, L1, and L2 nerve roots and showed 75% to 100% pain relief in all patients, lasting 6–9 months. Using PRF on nerve roots, however, requires fluoroscopic imaging and precise positioning of the needle, and is usually preceded by diagnostic nerve root blocks. While the pathophysiology of orchialgia is poorly understood, afferent innervation of the testis has been described [15]. Pain originating from testis and epididymis is mediated by sympathetic fibers that accompany the internal spermatic vessels. These fibers are then carried in the genital branch of genitofemoral nerve and ilioinguinal nerve. The autonomic supply is eventually distributed to the presacral ganglia of T10-L2 segments. Somatic fibers from the parietal and visceral layers of tunica vaginalis and cremaster are carried by the

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Pulsed Radiofrequency of Spermatic Cord

Conclusions

Chronic testicular pain remains an enigmatic condition. PRF of the spermatic cord offers a chance of cure for at least some patients presenting with chronic refractory testicular pain. It is an easy-toperform and safe procedure that can be repeated if

necessary. It does not preclude further surgical treatment. This promising treatment should be investigated further with placebo-controlled trials. Acknowledgment We gratefully acknowledge the assistance of David Crook, PhD, with the revision of the manuscript. References

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pain but did not routinely perform diagnostic spermatic cord blocks. We believed that a negative cord block might preclude a suitable patient from this potentially curative treatment, which was safe and easy to administer. A positive cord block to select patients may have improved the overall success rate of the procedure. Although PRF appears to be effective, little is known about how it modifies central and peripheral pain pathways. Neurobiology trials indicate that PRF and sham treatment have different biological effects [17–20]. Higuchi et al. [17] studied the effect of electrical fields on upregulation of intermediate early gene (IEG) expression and showed that application of PRF (but not continuous RF) at 38°C to dorsal ganglia of rats, led to increased expression of IEG product c-Fos protein, in neurons in the superficial laminae of the dorsal horn 3 hours after treatment. The presence of transcription factor c-Fos suggests that PRF impulses may be involved in the long-term changes in gene expression that underlie neuronal plasticity. Van Zundert et al. [18] investigated a possible delayed effect of PRF and found that c-Fos immunoreactive cells increased in both the PRF and continuous RF (67°C) groups at 7 days. These results support the hypothesis that the mode of action of PRF is not temperature dependent. In addition, Cahana et al. [21] demonstrated in a cell culture model that the acute effects of PRF are more reversible and less destructive than continuous RF even under nonthermal conditions. In an experiment by Podhajsky et al. [19] to examine the neuropathological effects of the technique, low-temperature RF led to inconsequential changes at light microscopic level although subclinical changes included endoneural edema, fibroblast activation, and collagen deposition. The changes in the peripheral nerve were short lived compared with the effect on DRG. Finally, it appears that PRF selectively targets neurons whose axons are composed of small diameter A delta and C fibers involved in nociception [22]. More research is needed to determine the exact mechanism of action and the optimal duration of treatment with PRF.

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