Nonselective innervation of lamina I projection neurons by cocaine- and amphetamine-regulated transcript peptide (CART)-immunoreactive fibres in the rat spinal dorsal horn

Diabetic neuropathic pain is often considered to be caused by peripheral neuropathy. The involvement of the CNS in this pathological condition has not been well documented. Development of hypersensitivity of spinal dorsal horn neurons is involved in neuropathic pain induced by traumatic nerve injury. In the present study, we determined the functional changes of identified spinothalamic tract (STT) neurons and their correlation to diabetic neuropathic pain. Diabetes was induced in rats by intraperitoneal injection of streptozotocin. Hyperalgesia and allodynia were assessed by the withdrawal responses to pressure, radiant heat, and von Frey filaments applied to the hindpaw. Single-unit activity of STT neurons was recorded from the lumbar spinal cord in anesthetized rats. The responses of STT neurons to mechanical and thermal stimuli and the sensitivity to intravenous morphine were determined in diabetic and normal rats. In 12 diabetic rats, mechanical allodynia and hyperalgesia, but not thermal hyperalgesia, developed within 2 wk after streptozotocin injection and lasted for ≥7 wk. Compared to the 32 STT neurons recorded in normal animals, the 37 STT neurons in diabetic rats displayed a higher spontaneous discharge activity and enlarged receptive fields. Also, the STT neurons in diabetic rats exhibited lower thresholds and augmented responses to mechanical stimulation. Intravenous injection of 2.5 mg/kg of morphine suppressed significantly the responses of STT neurons to noxious stimuli in 12 nondiabetic rats. However, such an inhibitory effect of morphine on the evoked response of STT neurons was diminished in 14 diabetic animals. This electrophysiological study provides new information that development of hypersensitivity of spinal dorsal horn projection neurons may be closely related to neuropathic pain symptoms caused by diabetes. Furthermore, the attenuated inhibitory effects of morphine on evoked responses of STT neurons in diabetes likely accounts for its reduced analgesic efficacy in this clinical form of neuropathic pain.

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Ultrastructural demonstration of direct enkephalinergic input onto medullary and spinal dorsal horn projection neurons

Pain ◽

10.1016/0304-3959(81)90223-2 ◽

1981 ◽

Vol 11 ◽

pp. S19 ◽

Cited By ~ 3

Author(s):

M. A. Ruda

Keyword(s):

Dorsal Horn ◽

Spinal Dorsal Horn ◽

Projection Neurons ◽

Spinal Dorsal

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Electrical properties of acutely isolated, identified rat spinal dorsal horn projection neurons

Neuroscience Letters ◽

10.1016/0304-3940(87)90267-9 ◽

1987 ◽

Vol 82 (3) ◽

pp. 267-272 ◽

Cited By ~ 20

Author(s):

Li-Yen Mae Huang

Keyword(s):

Electrical Properties ◽

Dorsal Horn ◽

Spinal Dorsal Horn ◽

Projection Neurons ◽

Spinal Dorsal

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A subset of spinal dorsal horn interneurons crucial for gating touch-evoked pain-like behavior

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2021220118 ◽

2021 ◽

Vol 118 (3) ◽

pp. e2021220118

Author(s):

Ryoichi Tashima ◽

Keisuke Koga ◽

Yu Yoshikawa ◽

Misuzu Sekine ◽

Moeka Watanabe ◽

...

Keyword(s):

Neuropathic Pain ◽

Dorsal Horn ◽

Spinal Dorsal Horn ◽

Viral Vectors ◽

Behavioral Responses ◽

Lamina I ◽

Spinal Dorsal ◽

Low Threshold ◽

Novel Strategy ◽

Aβ Fibers

A cardinal, intractable symptom of neuropathic pain is mechanical allodynia, pain caused by innocuous stimuli via low-threshold mechanoreceptors such as Aβ fibers. However, the mechanism by which Aβ fiber-derived signals are converted to pain remains incompletely understood. Here we identify a subset of inhibitory interneurons in the spinal dorsal horn (SDH) operated by adeno-associated viral vectors incorporating a neuropeptide Y promoter (AAV-NpyP+) and show that specific ablation or silencing of AAV-NpyP+ SDH interneurons converted touch-sensing Aβ fiber-derived signals to morphine-resistant pain-like behavioral responses. AAV-NpyP+ neurons received excitatory inputs from Aβ fibers and transmitted inhibitory GABA signals to lamina I neurons projecting to the brain. In a model of neuropathic pain developed by peripheral nerve injury, AAV-NpyP+ neurons exhibited deeper resting membrane potentials, and their excitation by Aβ fibers was impaired. Conversely, chemogenetic activation of AAV-NpyP+ neurons in nerve-injured rats reversed Aβ fiber-derived neuropathic pain-like behavior that was shown to be morphine-resistant and reduced pathological neuronal activation of superficial SDH including lamina I. These findings suggest that identified inhibitory SDH interneurons that act as a critical brake on conversion of touch-sensing Aβ fiber signals into pain-like behavioral responses. Thus, enhancing activity of these neurons may offer a novel strategy for treating neuropathic allodynia.

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