Superiority of capsaicin 8% patch versus oral pregabalin on dynamic mechanical allodynia in patients with peripheral neuropathic pain

BackgroundDynamic Mechanical Allodynia (DMA) is a typical symptom of neuropathic pain (NP). In a recent study, the capsaicin 8% patch was noninferior to pregabalin in overall peripheral NP relief. In this study, we report the comparison of the two treatments in relieving DMA. MethodsIn a randomized, open-label, head-to-head, 8-week study, 488 patients with peripheral NP were treated with the capsaicin 8% patch (one application) or an optimized dose of pregabalin. Assessments included the area and intensity of DMA, and the number of patients achieving complete resolution of DMA. ResultsAt baseline, 253 patients in the capsaicin 8% patch group and 235 patients in the pregabalin group had DMA. From baseline to end of study, the change in DMA intensity was significantly in favour of the capsaicin 8% patch versus pregabalin [-0.63 (95% CI: -1.04, -0.23; p=0.002)]. Similarly, the capsaicin 8% patch was superior to pregabalin in reducing the area of DMA [-39.5cm(2) (95% CI: -69.1, -10.0; p=0.009)] from baseline to end of study. Overall, a greater proportion of patients had a complete resolution of allodynia with capsaicin 8% patch treatment compared with pregabalin treatment (24.1% vs. 12.3%; p=0.001) at end of study. ConclusionCapsaicin 8% treatment was superior to pregabalin in reducing the intensity and area of DMA, and in the number of patients with complete resolution of DMA. SignificanceThe superiority of a topical treatment over pregabalin in relieving DMA supports the view that both peripheral and central sensitization can mediate allodynia.Peer reviewe

Contralateral hyperalgesia and allodynia following intradermal capsaicin injection in man

Objectives. Contralateral responses to unilateral stimuli have been well described in animal models. These range from central sensitization to peripheral inflammatory responses. Our aim was to test for contralateral responses following unilateral intradermal capsaicin injection in man

Norepinephrine-evoked pain in fibromyalgia. A randomized pilot study [ISRCTN70707830]

BACKGROUND: Fibromyalgia syndrome displays sympathetically maintained pain features such as frequent post-traumatic onset and stimuli-independent pain accompanied by allodynia and paresthesias. Heart rate variability studies showed that fibromyalgia patients have changes consistent with ongoing sympathetic hyperactivity. Norepinephrine-evoked pain test is used to assess sympathetically maintained pain syndromes. Our objective was to define if fibromyalgia patients have norepinephrine-evoked pain. METHODS: Prospective double blind controlled study. Participants: Twenty FM patients, and two age/sex matched control groups; 20 rheumatoid arthritis patients and 20 healthy controls. Ten micrograms of norepinephrine diluted in 0.1 ml of saline solution were injected in a forearm. The contrasting substance, 0.1 ml of saline solution alone, was injected in the opposite forearm. Maximum local pain elicited during the 5 minutes post-injection was graded on a visual analog scale (VAS). Norepinephrine-evoked pain was diagnosed when norepinephrine injection induced greater pain than placebo injection. Intensity of norepinephrine-evoked pain was calculated as the difference between norepinephrine minus placebo-induced VAS scores. RESULTS: Norepinephrine-evoked pain was seen in 80 % of FM patients (95% confidence intervals 56.3 – 94.3%), in 30 % of rheumatoid arthritis patients and in 30 % of healthy controls (95% confidence intervals 11.9 – 54.3) (p < 0.05). Intensity of norepinephrine-evoked pain was greater in FM patients (mean ± SD 2.5 ± 2.5) when compared to rheumatoid arthritis patients (0.3 ± 0.7), and healthy controls (0.3 ± 0.8) p < 0.0001. CONCLUSIONS: Fibromyalgia patients have norepinephrine-evoked pain. This finding supports the hypothesis that fibromyalgia may be a sympathetically maintained pain syndrome

Derangement of body representation in complex regional pain syndrome: report of a case treated with mirror and prisms

Perhaps the most intriguing disorders of body representation are those that are not due to primary disease of brain tissue. Strange and sometimes painful phantom limb sensations can result from loss of afference to the brain; and Complex Regional Pain Syndrome (CRPS)—the subject of the current report—can follow limb trauma without pathology of either the central or peripheral nervous system. This enigmatic and vexing condition follows relatively minor trauma, and can result in enduring misery and a useless limb. It manifests as severe pain, autonomic dysfunction, motor disability and ‘neglect-like’ symptoms with distorted body representation. For this special issue on body representation we describe the case of a patient suffering from CRPS, including symptoms suggesting a distorted representation of the affected limb. We report contrasting effects of mirror box therapy, as well as a new treatment—prism adaptation therapy—that provided sustained pain relief and reduced disability. The benefits were contingent upon adapting with the affected limb. Other novel observations suggest that: (1) pain may be a consequence, not the cause, of a disturbance of body representation that gives rise to the syndrome; (2) immobilisation, not pain, may precipitate this reorganisation of somatomotor circuits in susceptible individuals; and (3) limitation of voluntary movement is neither due to pain nor to weakness but, rather, to derangement of body representation which renders certain postures from the repertoire of hand movements inaccessible

Regulation of peripheral blood flow in Complex Regional Pain Syndrome: clinical implication for symptomatic relief and pain management

Background. During the chronic stage of Complex Regional Pain Syndrome (CRPS), impaired microcirculation is related to increased vasoconstriction, tissue hypoxia, and metabolic tissue acidosis in the affected limb. Several mechanisms may be responsible for the ischemia and pain in chronic cold CPRS. Discussion. The diminished blood flow may be caused by either sympathetic dysfunction, hypersensitivity to circulating catecholamines, or endothelial dysfunction. The pain may be of neuropathic, inflammatory, nociceptive, or functional nature, or of mixed origin. Summary. The origin of the pain should be the basis of the symptomatic therapy. Since the difference in temperature between both hands fluctuates over time in cold CRPS, when in doubt, the clinician should prioritize the patient's report of a persistent cold extremity over clinical tests that show no difference. Future research should focus on developing easily applied methods for clinical use to differentiate between central and peripheral blood flow regulation disorders in individual patients