Wide Dynamic Range (WDR) Neurons
Wide dynamic range (WDR) neurons are specialized neurons in the spinal dorsal horn that respond to a wide range of innocuous and noxious mechanical stimuli, encoding stimulus intensity through changes in their firing rate. 1, 2
Characteristics of WDR Neurons
Location and Distribution
- Primarily located in laminae IV-VI of the spinal dorsal horn 3
- First major pain relay station in the central nervous system 1
- Process information from peripheral afferents before transmission to higher brain centers
Functional Properties
- Respond to both non-noxious and noxious stimuli 1, 2
- Encode stimulus intensity as changes in firing rate 2
- Have complex responses to peripheral nerve stimulation with nonlinearities and history effects 1
- Possess large receptive fields that can expand in pathological pain states 4
Response Patterns
- C-fiber responses consist of three components: early, middle, and late 3
- Exhibit "windup" phenomenon (increased responsiveness to repeated stimulation), particularly in the middle and late components 3
- Respond to various sensory modalities including mechanical, thermal, and chemical stimuli 2
Role in Pain Processing
Normal Pain Transmission
- Encode intensity of mechanical stimuli through changes in firing rate 2
- Transmit information to higher brain centers including the thalamus, somatosensory cortex, and limbic structures 5
- Integrate information from multiple peripheral inputs 1
Pathological Pain States
Show increased excitability in neuropathic pain models 4
- Enlarged receptive field size
- Increased spontaneous activity
- Decreased C-response threshold and latency
- Increased C-response duration
Consistent increase in spontaneous firing rate in multiple pain models:
- Neuropathic pain
- Arthritis and inflammation
- Chemoneuropathy 2
Clinical Significance
Role in Sympathetically Maintained Pain
- WDR neurons are the primary spinal nociceptive neurons activated by sympathetic efferent activity 6
- Nearly half (45%) of WDR neurons can be activated by sympathetic stimulation 6
- Sympathetic activation of WDR neurons is mediated by an alpha-adrenergic mechanism in the skin 6
Implications for Pain Treatment
- WDR neurons are potential targets for neuromodulation treatments for chronic pain 1
- Understanding WDR neuron responses may help improve electrical nerve stimulation therapies 1
- Inhibiting hyperexcitability of WDR neurons to C-fiber input could lead to treatments for neuropathic pain 3
Neurophysiological Monitoring
- WDR neuron activity can be modeled using linear parameter varying (LPV) models to capture responses to peripheral nerve stimulation 1
- These models may help design closed-loop peripheral nerve stimulation for pain treatment 1
- Electrophysiological recordings can identify changes in WDR neuron function in pathological states 4
Understanding WDR neurons is crucial for developing effective pain management strategies, particularly for conditions involving central sensitization and neuropathic pain mechanisms.