Phototherapy Could Thwart Neuropathic Pain

Low-level laser therapy could provide a noninvasive and effective method for treating neuropathic pain caused by nerve damage, spinal cord injury or diseases such as diabetes.

In studies performed at the Biomedical Science Institute (ICB-USP) in Brazil, laser therapy was tested in three models of neuropathic pain using rats. Behavioral responses improved in all three models. The results of the studies suggest that all three models shared a common response to the laser therapy which included myelin sheath regeneration and reduced astrocyte migration to the site of the inflammation.

In the first study, to induce a condition similar to type 1 diabetes in humans, rats were injected with streptozotocin (STZ). After a period of time, the rats were irradiated with a GaAs laser emitting a wavelength of 904 nm, an output power of 45 mWpk, beam spot size at target 0.13 cm², a frequency of 9500 Hz, a pulse time 60 ns, and an energy density of 6,23 J/cm².

“We began the treatment after 45 days, when the neuropathic condition was well-established and had become chronic,” said professor Marucia Chacur. “We used a 904-nm laser, which can penetrate deep into tissue.”

The degree of pain was evaluated before and after the start of treatment using behavioral tests such as the von Frey hair test. The researchers found that four sessions of low-level laser therapy was sufficient to reverse allodynia and protect peripheral nerve damage in diabetic rats.

“We plan to apply the technique to humans, so we used similar therapeutic protocols,” Chacur said. “We initially scheduled ten sessions of phototherapy applied to the thigh every ten days, each lasting one minute, but we observed an improvement shortly after the fourth session.”

With the aid of a transmission electron microscope, the researchers found that as diabetes progressed, the structure of the sciatic nerve's myelin sheath changed. After four sessions of the treatment, however, the myelin had almost completely recovered.

“The condition of the nerve practically returned to baseline levels after treatment. We’re now continuing the study by analyzing protein expression and the release of inflammatory cytokines to understand exactly what’s happening,” Chacur said.

In a second study, treatment again focused on the sciatic nerve, but the injury was induced by compression to simulate what happens in patients with spinal stenosis or disc herniation.

“The nerve was ligated and kept compressed for two weeks until the injury became chronic. Phototherapy began on the 14th day,” Chacur explained. “Shortly after the second session, we observed a behavioral improvement, which persisted until the end of the treatment.”

Researchers analyzed the rats’ dorsal root ganglion using immunoblotting to scan for the presence of astrocytes. The analysis showed smaller numbers of astrocytes in rats treated with laser therapy than in untreated rats.

“Astrocytes are the first type of cell to migrate to the site of a nerve injury or inflammatory process,” Chacur said. “They're like a sort of macrophage for the central nervous system, the first line of defense.

“These cells release several inflammatory mediators, including interleukin-1 (IL1), tumor necrosis factor alpha (TNF-a) and glutamate. These mediators in turn trigger the release of other inflammatory substances. We believe the laser curtails this chain reaction as if it were anti-inflammatory medication, by reducing the migration of astrocytes to the site of the injury,” said Chacur, adding that the next step is to measure the concentration of each inflammatory substance separately.

The third model used to test low-level laser therapy focused on orofacial pain. In this model, a lesion was induced by crushing the inferior alveolar nerve, one of the branches of the trigeminal nerve responsible for innervating the face.

“This type of injury can occur during extraction of a wisdom tooth, for example. Many dentists are using low-level laser therapy for patient pain relief,” Chacur said.

Phototherapy began two days after the nerve was injured. An improvement in pain-related behavior was observed after two sessions and persisted throughout the treatment, which comprised ten sessions (one every two days). The treated tissue was then analyzed for the presence of certain proteins.

“We set out to understand the mechanisms and mediators involved because we believed phototherapy could be used in association with pharmacological treatment because it acts via a different pathway. In this way, it may be possible to reduce the drug dose and mitigate the systemic effects of the treatment,” Chacur said.

“Evidence in the literature also suggests an effect on mitochondria. The laser apparently facilitates the flow of calcium in these organelles, boosting production of ATP [adenosine triphosphate, the body's cellular fuel] and leading to enhanced healing as well as the release of mediators that assist remodeling. In future studies, we plan to investigate this effect on mitochondria more thoroughly,” Chacur concluded.

Although phototherapy’s efficacy in reversing painful stimuli and protecting nerve fibers from damage was demonstrated, this treatment protocol must be further evaluated in biochemical levels to confirm its biological effects.

The research was published in Lasers in Medical Science (doi: 10.1007/s10103-016-2140-3).