Background: Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes
and more than half of the patients with DPN have self-reported symptoms referring to painful
diabetic neuropathy (PDN). Nerve growth factor (NGF) is a key factor for the nervous system, but the
role of it in the neuropathic pain of diabetic patients is unclear.
Objective: This study aimed to investigate the relationship between the dynamic expression of
NGF in dorsal horn and dorsal root ganglion (DRG) of diabetic rats and hyperalgesia and allodynia in
diabetic neuropathic pain. It also aimed to explore the effects of exogenous mouse NGF (mNGF) on
NGF expression in dorsal horn, DRG, and mechanical pain threshold.
Study Design: Animal research study.
Setting: Experimental research laboratory.
Methods: The model of diabetes was established by a single intraperitoneal injection of streptozocin
(STZ 55 mg/kg). Firstly, the rats were randomly divided into 2 groups: control group (n = 10) and
diabetes group (n = 40). The diabetes group contained 4 subgroups: diabetes week 1 group (DM1,
n = 10), diabetes week 2 group (DM2, n = 10), diabetes week 4 group (DM4, n = 10), and diabetes
week 8 group (DM8, n = 10). Then, the other rats were randomly divided into 2 groups: control
group (n = 10) and treatment group (n = 30). The treatment group contained 3 subgroups: saline
group (n = 10), low dose mNGF group (mNGF1, n = 10), and high dose mNGF group (mNGF2, n =
10). Mechanical pain threshold was assessed using Von Frey hairs, before the establishment of the
diabetes model and 1, 2, 4, and 8 weeks after the establishment. The NGF expression in dorsal horn
and DRG was measured by western blot.
Results: The mechanical pain threshold decreased one week after the establishment of the diabetes
model, which continued for 8 weeks. The NGF expression in the dorsal horn was reduced 2 weeks
after diabetes induction and the decreased NGF expression continued for 4 weeks. However, the
NGF expression in DRG was reduced one week after diabetes induction and remained at a low level
for 8 weeks. Hyperalgesia occurred when the NGF expression in the DRG decreased and further
reduction in the NGF expression in the dorsal horn caused concomitant allodynia. The mechanical
pain threshold was significantly elevated 2 weeks after mNGF treatment.
Limitations: The course of diabetes should be much longer and there is not a precise analysis
of the quantitative relation between the NGF expression in the dorsal horn/DRG and hyperalgesia/
allodynia.
Conclusion: In diabetic neuropathic pain, the dynamic changes of the NGF expression in dorsal
horn and DRG is involved in the development of hyperalgesia and allodynia respectively. Exogenous
mNGF may relieve diabetic neuropathic pain by increasing the NGF expression in dorsal horn and
DRG.
Key words: Nerve growth factor, diabetic peripheral neuropathy, pain, hyperalgesia, allodynia,
dorsal horn, dorsal root ganglion
Pain Physician 2017; 20:E551