In order to investigate the possible relationship between chronic pain
and the immune system, delayed-type hypersensitivity (DTH) and humora
l immunity were assessed in Sprague-Dawley rats subjected to unilatera
l peripheral mononeuropathy induced by sciatic ligation. Paw withdrawa
l latency (PWL) time was measured twice during the experiment in anima
ls subjected to sciatic nerve ligation or sham surgery. Sciatic nerve-
ligated animals showed hyperalgesia in the leg subjected to neural lig
ation when compared to the contralateral leg. No differences in PWL ti
mes existed in sham-operated animals. In order to exclude possible alt
erations in immune response due to the surgical procedure or to the hy
peralgesia testing, a group of control animals, not subjected to surgi
cal procedures or hyperalgesia testing, was also included in the exper
iment. Three days post-sciatic ligation or sham surgery, both experime
ntal and control animals were sensitized to keyhole limpet hemocyanin
(KLH). A secondary sensitization followed 1 week after the initial imm
unization. Fourteen days after the initial sensitization, KLH was inje
cted into the hind foot pad and vehicle into the contralateral foot pa
d in order to assess DTH. One group of rats subjected to sciatic nerve
ligation was tested for DTH in the hind foot pad ipsilateral to the l
igated nerve, while another group was tested in the contralateral foot
pad. Twenty-four hours following foot pad injections, the thickness o
f both paws was measured and animals were bled to test for anti-KLH im
munoglobulins. Animals in which mononeuropathy was induced, but not sh
am-operated or control animals, exhibited an enhanced DTH response to
KLH. This enhanced DTH response occurred both ipsilateral and contrala
teral to the ligated nerve. This increased response was blocked in bot
h cases by the local anesthetic bupivicaine. Two sham-surgery groups a
nd a normal control group were tested similarly. Gamma-immunoglobulin
levels against KLH were significantly reduced in the hyperalgesic anim
als when compared to control animals but were similar when compared to
sham-operated animals. This study suggests that chronic nociception c
auses significant alterations in immune function and strengthens the h
ypothesis that chronic pain can influence the immune system.