Masamichi Goto,

Yukiko Sugio,

Seiichi Sawada,

Yuichiro Yoshinaga,

Takahiro Miyauchi,

Hiroshi Masuda

National Sanatorium

Hoshizuka-Keiaien

4204 Hoshizukacho,

Kanoya city

Kagoshima 893-8502,

Japan

EFFECT OF PREGABALIN ON THE CHRONIC NEUROPATHIC PAIN

OF LEPROSY

the 18th International Leprosy Congress 18/09/2013

Session Title: Nerve Injury in Leprosy O-156

• In Japan, 27% of the individuals with cured leprosy

suffered from chronic neuralgia (cross sectional study in

1995). They typically occur in cold environment and

before rain, and relevant nerve trunks show mild pain on

pressure. As they are not active neuritis, steroid is

ineffective. NSAIDs and vitamin B12 have been used yet

with limited effects.

INTRODUCTION

Perineurium

Myelinated axon

Myelinated Schwann cell

Distribution of

M. leprae in the

peripheral

nervous system Unmyelinated axon

Unmyelinated Schwann cell

Endoneurium

Dorsal root

ganglia

Blood Vessel

Macrophage

CNS involvement:

J Neuropathol

Exp Neurol 2007;

66: 284-294

Nerve injury due to type 1 (upgrade) reaction

preserved nerve

Nerve swelling and destruction by

granulomatous inflammation

from Leprosy, Science working towards dignity, Tokai Univ. Press 2011

Type 1

reaction in

BL leprosy

(sural nerve)

Nerve injury due to type 1 (upgrade) reaction

from Leprosy, Science working towards dignity, Tokai Univ. Press 2011

Lepromatous

leprosy with long

history

of treatment

Trigeminal nerve

with severe

neuralgia showing

mild lymphocytic

infiltration

(Dr. Nogami's case)

Cured

lepromatous

leprosy

Dense fibrosis of

nerve bundle

Neuropathic pain and pregabalin

• Pregabalin is a calcium channel alpha2delta ligand that is effective against neuropathic pain such as post-herpetic neuralgia and diabetic neuropathy by blocking the hyperexcitability of neurons in the spinal dorsal horn.

• Since post-herpetic neuralgia and chronic neuralgia in leprosy are both inflammatory neuropathies, pregabalin might be effective in the latter condition.

Nerve injury

hyperresponse

microglia

microglia amygdala

insular cortex

somatosensory area

Modified from Nagai J, Nagasaki Univ. 2011

• In 2011, we started to use pregabalin in our leprosy

sanatorium ( 199 residents, average age, 82 y.o.).

• 21 patients with chronic neuralgia (13 males, 8 females,

age 83+7, body weight 50+8 kg) have received pregabalin

(LILICA) with mean daily dose of 60mg (25-150mg).

• Pretreatment renal function was estimated by estimated

creatinine clearance (Clcr). 13% of the 12 patients were

60

Table 1. Basic data of pregabalin-treated individuals

Gender Male Female

n 13 8

Age 83.7 ± 8.9 83.8 ± 5.3

Height (㎝) 154.0 ± 7.5 133.9 ± 7.0

B.W. (kg) 50.5 ± 10.7 48.9 ± 7.1

Creatinine (㎎/dl) 0.9 ± 0.2 0.7 ± 0.2

Creatinine Clearance

(Clcr, ml/min) 49.2 ± 23.4 51.3 ± 23.3

eGFR 66.7 ± 21.4 67.1 ± 25.8

Unadjusted eGFR 57.4 ± 22.3 52.6 ± 20.9

Disease type (cured) L/BT=10/3 L/BT=6/1

90%

5% 5%

Effect of pregabalin

effective

no effect

unknown

0% 20% 40% 60% 80% 100%

Detail unkown

Decrease of self injury

Better sleep

Decrease of NSAIDsusage

Decrease of pain

Loss of pain

Analysis of effectiveness

+

-

unknown

Fig. 2

Effect of pregabalin on the chronic neuropathic pain of leprosy

Fig. 1

0% 20% 40% 60% 80% 100%

Disorient…

Weakness

Fatigue

Abnormal…

Falling

Vague…

Headache

Drowsine…

Edema

Dizziness

Wobbline…

Adverse effects of pregabalin

+

-

Fig. 3

Adverse effects of pregabalin

Fig. 4 Care for adverse effects

Continue,

37%

Decrease,

27%

Stop,

27%

Decrease & stop,

9%

Analysis of renal function

Table 2. Recommended daily dose

Clcr

（ml/min）

Initial

dose

（mg）

Maintenance

dose

（mg）

Maximum

dose

（mg）

Clcr＜15 25 25－50 75

15≦Clcr＜30 25－50 75 150

30≦Clcr＜60 75 150 300

60≦Clcr 150 300 600

Fig. 5 Renal function of

pregabalin-treated cases

Clcr

Analysis of effective dose

0.00

0.50

1.00

1.50

2.00

2.50

0 5 10 15 20

Ratio of effective/recommended dose

Daily dose (Mean+SD) 61.4+39.3 mg

Max. dose 150 mg

Min. dose 25 mg

Prescription period

(Mean+SD)

163.2+111.

8 days

Max. period 311 days

Min. period 33 days

Table 3 Dose and period of pregabalin

Fig. 6

RESULTS

• Improvement of pain was observed in 19 of 21 (90%) cases.

• The effect appeared within a few days after starting the

administration, and loss of pain, decrease of pain, decrease

of NSAIDs usage and better sleep were observed.

• Due to advanced age and impaired renal function, typically

25mg of pregabalin before bedtime was sufficient (cf. usual

adult dose, 150mg/day). Major adverse effects were wobble

(67%) and dizziness (24%), and 38% of the patients could not

continue the drug.

CONCLUSION

• If the cured patients complain intractable pain of nerves

once involved by leprous neuritis and the nerves are

fibrosed, neuropathic pain should be considered.

• In such cases pregabalin could be an effective remedy.

Declaration

• I have no conflict of interest.