Post Herpetic Neuralgia: A Retrospective Study to Evaluate Response to Modified Jaipur Block with Increased Concentration of Dexamethasone.

BACKGROUND: Postherpetic neuralgia (PHN) is a complication of herpes zoster characterized by persistent dermatomal pain. It has a negative impact on the quality of life. There is no gold standard therapy for PHN, and various local and systemic treatments have been tried. There are studies reporting the use of combination of steroids and local anesthetics but there is no standardized method. AIM: To evaluate the response of modified Jaipur block with increased concentration of dexamethasone.
METHODS: We conducted a retrospective study in patients who were given Jaipur block. The patients age, sex, duration of PHN, type and severity of pain were observed. A combination of 2% lignocaine and 0.5% bupivacaine and dexamethasone was injected subcutaneously. The pain was scored using visual analogue scale at the baseline, and 1 month after 1st, 2nd, and 3rd session of block and follow up after 6 months and 1 year.
RESULTS: The mean age of our patient was 63.33 ± 9.5 years. The males outnumbered females. Thoracic dermatomes were more commonly involved. The mean duration of PHN was 11.58 ± 12.76 months; stimulus evoked PHN was the commonest type of pain seen. The mean visual analogue score (VAS) decreased progressively after each session of the block. Maximum patients (50%) had excellent response, whereas 1.9% did not respond to the block. Relapse of pain was seen in 5.6% of the patients. There was no significant side effect noted. LIMITATIONS: There was no objective method used to assess pain.
CONCLUSION: PHN is chronic neuropathic pain. Response to modified Jaipur block is good, but if the duration of PHN is more, the recurrence rate is higher. Modified Jaipur block is an effective and safe treatment for PHN. Copyright:

Introduction

Postherpetic neuralgia (PHN) is the commonest complication of herpes zoster reported in 20% cases.[1] Though the definition of PHN is not standardized, neuropathic pain associated with herpes zoster is classified into acute, subacute, and chronic with a duration of <1 month, 1–3 months, and >3 months, respectively.[2] PHN includes the subacute and chronic neuropathic pain. PHN is usually self-resolving pain; however, rarely, it may persist for more than a year in less than 5% cases and indefinitely in still fewer.[3] Major risk factor is immunosuppression which may be due to age, malignancy, HIV, diabetes, prolonged immunosuppressive drugs, etc., Various treatments have been tried in PHN, but none is universally accepted, and quite often multimodal therapy has to be given. There are studies of intralesional treatment with combination of steroids and local anesthetics, but there is no specific combination and concentration of drugs to be used.[4567] We conducted this retrospective study in a tertiary care hospital to see response of this combination therapy in our patients.

The aim of the study was to see the effect on mean pain score and the total response and recurrence of PHN after modified Jaipur block.

Methods

This study was a retrospective study. It is our departmental protocol that all patients of PHN not responding to 2 months of pregabalin/gabapentin are shifted to modified Jaipur block therapy if there is no contraindication (HIV positive cases, patients with hypersensitivity to lignocaine or dexamethasone, glaucoma (when ophthalmic dermatome was involved), coagulation abnormalities or patients on anticoagulants, bacterial infection of the skin of the affected dermatome or history of arrythmias, or patients not willing for injectable treatment. We analyzed records of cases of PHN who did not respond to 2 months of pregabalin/gabapentin. There were 68 patients recorded from January 2017 to December 2018. Two patients were HIV positive so were excluded, one patient had lignocaine sensitivity, there were five patients who were not willing for injectable treatment, eight patients did not come for regular follow-up so were not considered. So, finally records of 52 patients were included in the study and were analyzed.

Data regarding demography and clinical presentation was retrieved from the records. Data relating to duration of pain, and character of pain was observed. Duration of pain was divided into four groups: <6 months, 6–12 months, 12–18 months, and >18 months. Character of pain was divided into spontaneous and stimulus evoked pain; spontaneous pain was further divided into continuous and intermittent type. Severity of pain was assessed using the visual analogue scale (VAS) at the baseline, and 4 weeks after the first, second, and third injection and at 6 months and 1 year of follow up after completion of the treatment were. Pain was defined as mild when pain score was <3, moderate when 4–6, and severe when >7. Decrease in VAS score at each visit was calculated, the improvement was graded from 0 to 4: 0 when no improvement, 1 when <25%, 2 when 25%–50%, 3 when 50%–75%, and 4 when >75% improvement was seen. Remission was defined when VAS pain score was ≤2 at 6 months and 1 year follow up. Relapse was considered when pain score increased by 2 value from that after the third injection. Any side effects during the study period were recorded.

We prepared modified Jaipur block by mixing 6 mL of lignocaine 2% (manufactured by ALPA Labs), 5 mL of 5% bupivacaine (Anawin manufactured by Neon Labs), and 1.0 mL of dexamethasone (decadron manufactured by Wockhardt) in a vial. The involved dermatome was identified, scarred areas were avoided, and areas of maximum pain were identified. At these sites, 2 mL of this solution was injected subcutaneously with a maximum of 8–10 injections in one sitting. The procedure was repeated monthly three times if the pain persisted. After 6 months of follow up, three patients (5.7%) showed relapse of pain. No treatment was given even if worsening of PHN and minor side effects were observed.

The data were entered into excel spread sheet. Statistical analysis was done using Epi info 7.2.2 (Centre for disease control and prevention) All discrete variables were expressed as percentages or proportions. Continuous variables were presented in mean ± SD.

Results

We analyzed records of 52 patients with PHN who did not respond to 2 months of pregabalin and were shifted to modified Jaipur block. The mean age of our patients was 63.33 ± 9.5. The males outnumbered females, accounting for 69.2%. Thoracic dermatome were the commonest involved in 49.0% (n = 25) of the patients, followed by ophthalmic. The mean duration of PHN was 11.58 ± 12.76 months. We had maximum patients having duration of PHN less than 6 months (50%) [Figure 1]. A total of 42.

Figure 1

Distribution of patients according to duration of postherpetic neuralgia

3% of the patients had no comorbid conditions, 26.9% were hypertensive, and 13% were diabetic. Other co-morbid conditions were malignancies, bronchial asthma, arthritis, hypothyroidism, and cardiac diseases. Most common type of pain was stimulus evoked pain seen in 57.6% of the patients. Other types of pain seen were continuous and intermittent pain in 32.7%, and 9.7%, respectively [Table 1]. Maximum patients had severe pain as shown in Table 2. Mean VAS score at the start of modified Jaipur block was 7.730 ± 1.622. Mean VAS pain score decreased progressively after each session of modified Jaipur block [Figure 2], mean VAS pain score at end of 3 injections was 1.96 + 1.86. Improvement was graded after each session. Though some patients showed some improvement, 50% of the patients showed excellent response to three sessions of Jaipur block as shown in Table 3 [Figure 3]. There were only 1.94% of the patients with no significant improvement, and 5.77% had 25% reduction in pain. After 6 months of follow-up, three patients (5.7%) showed relapse of pain. There was no side effect seen except that one patient of PHN with diabetes developed injection site infection.

Table 1

Distribution of type of post herpetic neuralgia pain

Type of pain	Frequency	Percent
Continuous	17	32.69%
Intermittent	5	9.62%
Stimulus provoked	30	57.69%
Total	52	100.00%

Table 2

Distribution of patients according to severity of postherpetic neuralgic pain

GRADES	Frequency	Percentage
1	3	5.77%
2	6	11.54%
3	43	82.69%
Total	52	100.00%

Figure 2

Graph showing decline of mean VAS pain score after each session of block

Table 3

Grading of pain improvement 4 weeks after each session of block

Grade	1st injection		2nd injection		3rd injection
	n	%age	n	%age	n	%age
0	14	26.92	3	5.77%	1	1.92%
1	15	28.8	4	7.69%	3	5.77%
2	15	28.8	24	46.15%	9	17.31%
3	8	15.3	18	34.62%	13	25.00%
4	0	0	3	5.77%	26	50.00%

Figure 3

Showing grades of pain improvement after each session of block

Discussion

Postherpetic neuralgia (PHN) is a localized dermatomal neuropathic pain experienced 1 month after herpes zoster. Immunosuppression is the commonest risk factor for PHN. Broadly type of pain in PHN is divided into two broad categories spontaneous and stimulus evoked. Spontaneous pain can be either continuous (burning, aching, throbbing) or intermittent (stabbing, shooting, electric-shock-like pain). Stimulus-evoked pain can present as allodynia and hyperalgesia.[8] Allodynia is the commonest type of pain reported in PHN.[9] In our study, also allodynia was the commonest type of pain seen in 57.6% (n = 30) of the patients, followed by continuous pain in 32.7% of the patients.

PHN results due to interplay between various central and peripheral mechanisms. Herpes zoster infection leads to deafferentation (damage to myelin sheath and axons and replacement by fibrosis). Deafferentation of small fibers leads to allodynia, whereas if both small and large fibers are involved, severe spontaneous pain results.[10] Nerve injury also leads to increased neuronal sodium channel expression, which creates an electrochemical environment, so the neurons reach their depolarization threshold rapidly. These irritable nociceptors in turn lead to heightened response in dorsal horn nucleus.[11] These along with decreased central inhibition lead to stimulus evoked allodynia and hyperalgesia with no sensory loss. The threshold for heat activation of C nociceptors in the skin decreases due to changes in thermal gating of heat-sensitive transducer channels including TRPV1. This leads to heat allodynia even at the normal body temperature.[12] Also, studies have shown increased IL-8 in cerebrospinal fluid and in nerves.[1314]

There are multiple mechanisms, which lead to the development of pain in PHN so are the treatment modalities. Various treatments have been tried, but none is universally effective. Various anticonvulsants used are calcium channel α 2δ ligands (gabapentin and pregabalin), oxacarbazepine, levetiracetam, etc., Topical lignocaine and capsaicin patches, lignocaine infusions are effective but are shorter acting treatments. Interventional treatments like epidural, paravertebral block, stellate ganglion block, and sympathetic block in which local anesthetics alone or in combination with steroids have been used for patients not responding to the above treatments.[15] There are certain other treatments like prostaglandins, ATP, and pulsed radiofrequency which are in trial phase.[16] According to the FDA protocol, the use of anticonvulsants, tricyclic antidepressants, and a 5% lidocaine patch are the first line treatments, and opioids/topical capsaicin patch or cream are the second-line treatments for PHN.[17]

Different studies have used a combination of steroids and local anesthetics by subcutaneous injection [Table 4]. The concentration of these injectables were different in each study. We used a higher amount of dexamethasone (4 mg/mL) with 2% lignocaine and 0.5% bupivacaine in a ratio of 1:5:5 and evaluated the decrease in pain in our study.

Table 4

Comparison in different parameters in various studies using intralesional injections for treatment of post herpetic neuralgia

Name of study	Combination used	Maximum patients in age group/mean age in years	Sex	Commonest dermatome	duration of PHN in maximum patients (in months)	Duration >2 years	Mean VAS at baseline	Response rate
Bhargava et al.[4]	L: B: D: 3:2:0.02 freq 6 weeks	60–80 (48%)	-	Thoracic (57%)	0–6 (47%)	12%		85%%
Puri et al.[5]	L, B, D Concentration not mentioned, 6 weekly	41–50 (33.3%)	M>F	Lumbo-sacral (60%)	6–12 (40%)	10%		90%
Amjad et al.[6]	T: L: W: 1:5:44, 2 weekly	61.06	M>F					83.3%
Ni et al.[7]	T2:L2::1:1 3 weekly	65.86	F>M	Thoracic 62%				Response better than 2% L
Asim et al.[18]	T: W::3:7	45.93	M>F	Thoracic 20.68%			6.93
Khallid et al.[19]	6 weekly							60.2%
Epstein et al.[20]	T only 2 weekly							62.5%
Our study	L: B: D::6:5:1	63.33±9.53 years	M>F	Thoracic (49%)	0–6 (50%)		7.730±1.622	50% excellent, 25% good response

L (Lignocaine 2%), B (Bupivacaine 5%), D (Dexamethasone 4 mg/mL), T (Triamcinolone 40 mg/mL), T2 (triamcinolone 10 mg/mL), L2 (lignocaine 0.5%)

The various comparative parameters in different studies where intralesional/subcutaneous treatment were used are as shown in Table 4. Allodynia was the commonest type of pain experienced by our patients.

In our study, there were 1.9%of the patients who showed no improvement, and 5.77%, who showed slight improvement. Bhargava et al.[4] using Jaipur block reported response in 85% of the patients at 3 months and 96%, at 4 months. Puri et al.[5] reported 10%of the patients as poor responders. In a study, where patients were treated by the combination of triamcinolone with lignocaine 96% of the patients responded.[7] Amjad M treated patients with combination of triamcinolone and lignocaine, and they reported improvement in 63% of the patients after the first and 83.3%, after the second injection, whereas 16.7%, did not respond.[6] Asim et al.[18] reported a response is better with triamcinolone injection than lignocaine alone. Khallid et al. reported improvement in 60.2% of the patients at 12 weeks and 82%, at 18 weeks.[19] Epstein et al.[20] used only triamcinolone every fortnight observed response in 62.5%.

We observed excellent response in 50% of the patients, and another 25% had grade 3 response to treatment. Whereas Puri et al.[5] reported 20% of the patients had complete relief of pain after the first injection, 60% after the second injection, and 10% patients had complete relief of pain after the third injection. Bhargava et al.[4] reported response after each injection being in 28%, 57%, and 11% of the patients. None of the studies have mentioned about the type of PHN, the lesser response in our study could be because of deafferentation. Also PHN of longer duration is also less responsive to treatment

Bhargava et al.[4] reported no recurrence of pain on follow-up. Another study by Ni et al. reported a recurrence of 4%.[7] We followed our patients for 1 year. A total of 5.7% of the patients who had improvement after modified Jaipur block had recurrence of pain.

In our study, there was a single patient, a known diabetic, who developed wound site infection. In an Indian study, giddiness was the most common side effect seen in 10% of the patients followed by sweating in 6.6%.[5] Pain and hemorrhage at the injection site were observed by 16% of the patients by Ni et al.[6] Epstein because of use of higher concentration and more frequent administration observed cutaneous atrophy in 26% of the cases.[20]

In the original Jaipur block, the concentration of dexamethasone used was 0.16 mg/mL, whereas we used 0.32 mg/mL.[4] A higher concentration of steroids gives higher analgesic effect.[13] Amjad et al.[6] used triamcinolone in a concentration of 0.8 mg/mL combined with lignocaine. The benefit of combining steroids with local anesthetics are multiple, IL-8 is increased in cerebro spinal fluid and around nerves, which leads to inflammation and pain.[21] Steroids in subcutaneous tissue decrease IL-8 levels around the nerves. Also, stabilizing the membrane and suppressing ectopic discharges of c-fibers reduce central excitability.[22] The vasoconstriction caused by steroids prolongs the action of local anesthetics, also the intralesional steroid acts as a depot preparation. For a sustained action, we need a longer acting steroids, so dexamethasone is better than the intermediate acting steroids. Also local anesthetic injectables are usually acidic and hence cause stinging, dexamethasone having an alkaline pH prevents this side effect. Dexamethasone being a pure liquid has less chances of causing crystallization and atrophy than other particulate steroids.[23] Asim et al.[18] used 40 mg/mL triamcinolone diluted with normal saline in ratio of 30/70 mL without observing any side effects. Epstein et al.[20] used a higher dose of triamcinolone fortnightly, so had cutaneous atrophy in 26% of the cases.

Local anesthetics act by suppressing sodium channels and decreasing ectopic discharges, thus reducing membrane excitability.[24] Lignocaine has faster onset of action (2–3 min) of but the duration of action (2 h) in contrast bupivacaine though is slow to act but has a continued activity for longer time (4–8 h). There is no consensus on the concentration of anesthetics required, though few studies have reported a dose-related effect.[16] Various formulations like lignocaine patch (containing 700 mg of lignocaine), infusion, intrathecal/epidural injectables, and continuous epidural infusion are used. Intradermal therapy leads to faster onset of action, and the reservoir effect leads to sustained action with less systemic absorption. A higher dose of local anesthetics may cause arrythmias.

Limitations

We had no objective parameter for pain assessment. Pain threshold may not be the same in different people.

Conclusion

A combination of dexamethasone and local anesthetics gives a good response in stimulus-induced postherpetic neuralgia. To get a better response, modified Jaipur block should be started as a first line treatment in at least high risk patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.