Deficient conditioned pain modulation after spinal cord injury correlates with clinical spontaneous pain measures

Abstract

The contribution of endogenous pain modulation dysfunction to clinical and sensory measures of neuropathic pain (NP) has not been fully explored. Habituation, temporal summation, and heterotopic noxious conditioning stimulus-induced modulation of tonic heat pain intensity were examined in healthy noninjured subjects (n = 10), and above the level of spinal cord injury (SCI) in individuals without (SCI-noNP, n = 10) and with NP (SCI-NP, n = 10). Thermoalgesic thresholds, Cz/AFz contact heat evoked potentials (CHEPs), and phasic or tonic (30 seconds) heat pain intensity were assessed within the C6 dermatome. Although habituation to tonic heat pain intensity (0-10) was reported by the noninjured (10 s: 3.5 ± 0.3 vs 30 s: 2.2 ± 0.5 numerical rating scale; P = 0.003), loss of habituation was identified in both the SCI-noNP (3.8 ± 0.3 vs 3.6 ± 0.5) and SCI-NP group (4.2 ± 0.4 vs 4.9 ± 0.8). Significant temporal summation of tonic heat pain intensity was not observed in the 3 groups. Inhibition of tonic heat pain intensity induced by heterotopic noxious conditioning stimulus was identified in the noninjured (-29.7% ± 9.7%) and SCI-noNP groups (-19.6% ± 7.0%), but not in subjects with SCI-NP (+1.1% ± 8.0%; P < 0.05). Additionally, the mean conditioned pain modulation response correlated positively with Cz/AFz CHEP amplitude (ρ = 0.8; P = 0.015) and evoked heat pain intensity (ρ = 0.8; P = 0.007) in the SCI-NP group. Stepwise regression analysis revealed that the mean conditioned pain modulation (R = 0.72) correlated with pain severity and pressing spontaneous pain in the SCI-NP group. Comprehensive assessment of sensory dysfunction above the level of injury with tonic thermal test and conditioning stimuli revealed less-efficient endogenous pain modulation in subjects with SCI-NP.

Differential pain modulation properties in central neuropathic pain after spinal cord injury

“…29,35,37,38,79 Because nociceptive information ascending through the STTs triggers descending inhibitory control, 41 we hypothesized that damage to the STT after SCI is related to enhanced neuronal excitability and reduced descending pain inhibition, leading in turn to chronic CNP. Several findings support this hypothesis: (1) subjects with acute SCI who eventually developed CNP demonstrated a gradual increase in hyperexcitability concurrent with worsening of STT function towards CNP onset 80 ; (2) a recent study reported reduced pain inhibition among 10 CNP subjects with acute/subacute SCI 1 ; and (3) animal models of CNP after SCI revealed a decrease in the number of inhibitory GABAergic interneurons that correlated with neuropathic pain behavior 34,81 and a reversal of hyperexcitability by GABAergic agonists. 36,74 Because g-aminobutyric acid is involved in descending inhibition triggered by the STTs, these findings further support the association between damage to the STTs, reduction in descending controls, and resulting in hyperexcitability and chronic pain.…”

“…Pain inhibitory Table 2 Outcome results and group comparisons. July 2016 · Volume 157 · Number 7 www.painjournalonline.com 1419 mechanisms were recently examined by Albu et al 1 in a smaller group of subjects with CNP at the acute phase after SCI. They reported that subjects with and without CNP demonstrated lack of pain adaptation.…”

Pain Modulation: From Conditioned Pain Modulation to Placebo and Nocebo Effects in Experimental and Clinical Pain

“…Dysregulated spinal endogenous inhibitory systems and ongoing primary afferent activity are related to the intensity and duration of central sensitization (dorsal horn neuron hypersensitivity) present in neuropathic pain (Taylor, 2009). Psychophysical and electrophysiological approaches reveal impaired potency and duration of CPM in patients with postherpetic neuralgia (Pickering, Pereira, Dufour, Soule, & Dubray, 2014), in individuals with acquired neuropathic pain following spinal cord injury (Albu, Gómez-Soriano, Avila-Martin, & Taylor, 2015), in patients with painful diabetic polyneuropathy (DPN) of short duration (less than 2 years) (Granovsky, Nahman-Averbuch, Khamaisi, & Granot, 2017) and in cancer survivors with painful neuropathy acquired after chemotherapy (Nahman-Averbuch et al, 2011). The duration of DPN pain correlated positively with CPM efficacy, suggesting improvement of endogenous analgesia with chronicity of the pain syndrome (Granovsky et al, 2017).…”

Assessment and manifestation of central sensitisation across different chronic pain conditions

“…The CPM deficit has been shown to correlate with the severity in patients with spinal cord injury neuropathic pain (Albu et al, 2015) where the CPM deficit correlates positively with the number of painful body regions (Gruener et al, 2016), painful chemotherapy-induced polyneuropathy (NahmanAverbuch et al, 2011), complex-regional pain syndrome (Seifert et al, 2009), postherpetic neuralgia (Pickering et al, 2014), and traumatic peripheral nerve injury (Bouhassira et al, 2003).…”