The journal of pain : official journal of the American Pain Society
-
The present study examined the role of endogenous noradrenaline on glial and neuronal plasticity in the spinal cord in rats after peripheral nerve injury. An intrathecal injection of dopamine-β-hydroxylase antibody conjugated to saporin (DβH-saporin) completely depleted noradrenergic axons in the spinal cord and also reduced noradrenergic neurons in the locus coeruleus (A6) and A5 noradrenergic nucleus in the brainstem and noradrenergic axons in the paraventricular nucleus of the hypothalamus. DβH-saporin treatment itself did not alter mechanical withdrawal threshold, but enhanced mechanical hypersensitivity and intrathecal clonidine analgesia after L5-L6 spinal nerve ligation. In the spinal dorsal horn of spinal nerve ligation rats, DβH-saporin treatment increased choline acetyltransferase immunoreactivity as well as immunoreactivity in microglia of ionized calcium binding adaptor molecule 1[IBA1] and in astrocytes of glial fibrillary acidic protein, and brain-derived nerve growth factor content. DβH-saporin treatment did not, however, alter the fractional release of acetylcholine from terminals by dexmedetomidine after nerve injury. These results suggest that endogenous tone of noradrenergic fibers is not necessary for the plasticity of α2-adrenoceptor analgesia and glial activation after nerve injury, but might play an inhibitory role on glial activation. ⋯ This study demonstrates that endogenous noradrenaline modulates plasticity of glia and cholinergic neurons in the spinal cord after peripheral nerve injury and hence influences the pathophysiology of spinal cord changes associated with neuropathic pain.
-
Recent reports suggest deficits in conditioned pain modulation (CPM) and enhanced suprathreshold heat pain response (SHPR) potentially play a role in the development of chronic pain. The purpose of this study was to investigate whether central pain processing was altered in 2 musculoskeletal shoulder pain models. The goals of this study were to determine whether central pain processing: 1) differs between healthy subjects and patients with clinical shoulder pain; 2) changes with induction of exercise-induced muscle pain; and 3) changes 3 months after shoulder surgery. Fifty-eight patients with clinical shoulder pain and 56 age- and sex-matched healthy subjects were included in these analyses. The healthy cohort was examined before inducing EIMP, and 48 and 96 hours later. The clinical cohort was examined before shoulder surgery and 3 months later. CPM did not differ between the cohorts, however; SHPR was elevated for patients with shoulder pain compared to healthy controls. Induction of acute shoulder pain with EIMP resulted in increased shoulder pain intensity but did not change CPM or SHPR. Three months following shoulder surgery, clinical pain intensity decreased but CPM was unchanged from preoperative assessment. In contrast, SHPR was decreased and showed values comparable with healthy controls at 3 months. Therefore, the present study suggests that: 1) clinical shoulder pain is associated with measurable changes in central pain processing; 2) exercise-induced shoulder pain did not affect measures of central pain processing; and 3) elevated SHPR was normalized with shoulder surgery. Collectively our findings support neuroplastic changes in pain modulation were associated with decreases in clinical pain intensity only, and could be detected more readily with thermal stimuli. ⋯ Longitudinal studies involving quantitative sensory testing are rare. In exploring 2 musculoskeletal shoulder pain models (exercise-induced muscle pain and surgical pain), conditioned pain modulation was unchanged from pre- to post-assessment in both models. Suprathreshold heat pain response decreased after shoulder surgery and was comparable to healthy controls, suggesting this measure may be sensitive to decreases in clinical pain intensity.
-
The qualities of chronic neuropathic pain (NeP) may be informative about the different mechanisms of pain. We previously developed a 2-factor model of NeP that described an underlying structure among sensory descriptors on the Short-Form McGill Pain Questionnaire. The goal of this study was to confirm the correlated 2-factor model of NeP. Individual descriptive scores from the Short-Form McGill Pain Questionnaire were analyzed. Confirmatory factor analysis was used to test a correlated 2-factor model. Factor 1 (stabbing pain) was characterized by high loadings on stabbing, sharp, and shooting sensory items; factor 2 (heavy pain) was characterized by high loadings on heavy, gnawing, and aching items. Results of the confirmatory factor analysis strongly supported the correlated 2-factor model. ⋯ This article validates a model that describes the qualities of neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia. These data suggest that specific pain qualities may be associated with pain mechanisms or may be useful for predicting treatment response.
-
Randomized Controlled Trial
Test order of quantitative sensory testing facilitates mechanical hyperalgesia in healthy volunteers.
Quantitative sensory testing (QST) has become a widely used method to evaluate different submodalities of the somatic sensory system (predominantly) in patients with neuropathic pain. QST consists of 7 tests measuring 13 parameters in order to assess and quantify the perception of temperature, touch, pain, pressure, and vibration. The German Research Network on Neuropathic Pain implemented a standardized QST protocol including a defined testing order of the measurements. Accordingly, subjects tested with QST undergo thermal before mechanical testing. In the present study, we investigated the effect of testing order on the results of QST. Twenty healthy subjects were tested twice, 1 week apart with 2 different QST testing orders: the standardized testing order according to the German Research Network on Neuropathic Pain and a modified testing order in which mechanical stimuli were applied before thermal stimuli. For the test protocol that began with thermal testing, subjects exhibited signs of an increased mechanical perception: The mechanical pain sensitivity was significantly increased (P = .001, Wilcoxon test) for each pinprick stimulator and the mechanical pain threshold was lowered by a factor of 2 when compared with the modified testing order in which mechanical parameters were tested at the beginning of the session without prior thermal stimulation. Thermal parameters were the same for both test-order paradigms. These data indicate that preceding mild thermal stimulation might lead to a sensitization to mechanical stimuli and thus to mechanical hyperalgesia. Alternative habituation mechanisms in the modified testing order resulting from repeated pinprick stimulation at the beginning should also be debated. QST is a helpful diagnostic tool but interpretation should be done with consideration of interaction between test parameters. Reference data are only valid in the testing order from which they are obtained. ⋯ Present data showed that mechanical hyperalgesia followed thermal testing. This article demonstrates that the test order of quantitative sensory testing is relevant in interpreting the results obtained. Reference values are suitable in the test order from which they are obtained.
-
Evidence suggests that the effect of cigarette smoking on chronic pain is stronger in younger than older adults. This case-control study investigated whether age modified an effect of smoking on temporomandibular disorder (TMD) in 299 females aged 18 to 60 years. It also investigated the extent to which this relationship was explained by psychological profile, inflammatory response, and allergy. Cases were defined using the Research Diagnostic Criteria for Temporomandibular Disorders based on clinical examination. Psychological profile was evaluated using standardized instruments. Inflammatory response was evaluated with 11 cytokines isolated in plasma. History of allergy conditions was self-reported. Odds ratios (ORs) for the effect of smoking were calculated using binary logistic regression. Stratified analyses and the likelihood ratio test examined effect modification by smoking. Compared with nonsmokers, ever smokers aged <30 years had higher odds of TMD (OR = 4.14, 95% CI: 1.57, 11.35) than older adults (OR = 1.23, 95% CI: .55, 2.78) (P (effect modification) = .038). Adjustment for psychological profile, cytokines, and history of allergy-like conditions attenuated the effect by 45% to statistical nonsignificance. The main finding was reproduced with secondary analyses of 2 nationally representative surveys of adults conducted in the US and Australia. ⋯ This study showed that smoking was associated with TMD risk in females, but only in young adulthood. It replicated this finding in 2 nationally representative surveys of females in the US and Australia. Findings may alert clinicians to recognize that smoking is a concern for TMD in younger female patients.